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As regional diaphragmatic microvascular blood flow varies widely, the aim in this study was to estimate the number of repeated measurements, obtained by Laser-Doppler flowmetry (LDF), required to achieve a standard level of precision. In 40 urethane-anesthetized Sprague-Dawley rats, computer-aided LDF scanning coupled with a microscope generated diaphragmatic blood flow (Qdi) ranging between 94 and 944 mV with the frequency histogram displaying non-Gaussian distributions. A sampling technique was used to assess the number of measuring sites required for valid estimates of the regional diaphragmatic microvascular flow. From a total of 1,000 Qdi values, random samples of sizes between 5 and 100 were repeatedly drawn to estimate the variability of median flow. Our data shows that the 95th percentile decreased gradually, from a +30% error at n = 5 down to +20% at n = 15-20, remained between +20 and +15% up to n = 35, and reached +10% at n = 50. Moreover, by expressing the precision level of measurements as the length of a 95% confidence interval (beta), a linear relationship between beta values obtained either by the sampling method or repeated measures analysis of variance can be shown (r = 0.902, p < 0.001); beta values by either method were within +/-20% error of the mean values at sample sizes above n = 15. It is therefore recommended that for microscope-guided LDF scanning in the assessment of the distribution of diaphragmatic microvascular blood flow, at least 15 repeated measurements should be done to reach an acceptable standard level of precision. However, facing with clinical situations where 'blind' LDF scanning inevitably includes measurements over large vessels, the minimal sample sizes required to represent tissue perfusion demand further exploration.

Pulmonary microvessels (<70 microm) lack a complete muscular media. We tested the hypothesis that these thin-walled vessels do not participate in the hypoxic pressor response. Isolated canine lobes were pump perfused at precisely known microvascular pressures. A videomicroscope, coupled to a computerized image-enhancement system, permitted accurate diameter measurements of subpleural arterioles and venules, with each vessel serving as its own control. While vascular pressure was maintained constant throughout the protocol, hypoxia caused an average reduction of 25% of microvessel diameters. The constriction was reversed when nitric oxide was added to the hypoxic gas mixture. The nitric oxide reversal, combined with a lack of lobar blood flow redistribution as measured by fluorescent microspheres, shows that the constriction was active. This response suggests the unexpected potential for active intra-acinar ventilation-perfusion matching.

In emphysema, the diaphragm shortens by losing sarcomeres. We hypothesized that unless capillaries undergo a similar shortening, capillary geometry must be altered. Without quantifying this geometry, capillary length and surface area per fiber volume, which are critical measurements of the structural potential for blood-tissue exchange, cannot be resolved. Five months after intratracheal elastase (E) or saline (control; C) instillation, diaphragms from male Syrian golden hamsters were glutaraldehyde perfusion fixed in situ at reference lung positions (residual volume, functional residual capacity, total lung capacity) to provide diaphragms fixed over a range of sarcomere lengths. Subsequently, diaphragms were processed for electron microscopy and analyzed morphometrically. Emphysema increased lung volume changes from -20 to 25 cmH2O airway pressure (i.e., passive vital capacity) and excised lung volume (both P < 0.001). In each region of the costal diaphragm (i.e., ventral, medial, dorsal), sarcomere number was reduced (all P < 0.05). Capillary-to-fiber ratio increased (C = 2.2 +/- 0.1, E = 2.8 +/- 0.1; P < 0.01) and fibers hypertrophied (C = 815 +/- 35, E = 987 +/- 67 microns2; P < 0.05; both values at 2.5 microns sarcomere length). Capillary geometry was markedly altered by the loss of sarcomeres in series. Specifically, the additional capillary length derived from capillary tortuosity and branching was increased by 183% at 2.5 microns sarcomere length compared with C values (C, 359 +/- 43; E, 1,020 +/- 158 mm-2, P < 0.01). This significantly increased total capillary length (C, 3,115 +/- 173; E, 3,851 +/- 219mm-2 at 2.5 microns, P < 0.05) and surface area (C, 456 +/- 13; E, 519 +/- 24 cm-1, P < 0.05) per fiber volume. Thus emphysema substantially alters diaphragm capillary geometry and augments the capillary length and surface area available for blood-tissue exchange.

A 64-year-old man was admitted to our hospital with multiple hepatocellular carcinoma (HCC) lesions in the liver and lung. On the seventh hospital day, a chest radiograph showed a marked increase in right pleural effusion. A thoracentesis revealed a haemothorax. Despite repeated pleural taps and blood transfusions, the patient's clinical status worsened and he developed severe dyspnoea. An inferior phrenic arteriography on the 19th hospital day showed a tumour growing over the diaphragm into the right thoracic cavity, suggesting a tumour rupture. A transcatheter arterial embolization (TAE) of the inferior phrenic artery successfully controlled the bleeding and improved the haemothorax. There was no rebleeding; however, the patient died of advanced HCC 3 months later. To our knowledge, this is the first case of a haemothorax secondary to a ruptured HCC that was treated successfully with TAE.

1. The effects of N omega-nitro-L-arginine (L-NOARG) and N omega-nitro-L-arginine methyl ester (L-NAME) on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, L-arginine (L-arg) was used with the aim of preventing L-NOARG and L-NAME from inhibiting ACh-induced vasodilatation, in order to explore the possibility that L-NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. 2. Male Sprague-Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi-diaphragm of each rat was prepared and microvascular blood flow was recorded during continuous superfusion with bicarbonate-buffered prewarmed Ringer solution by using laser-Doppler flowmetry. The drugs were topically applied to the surface of the hemi-diaphragm. 3. Baseline microvascular blood flow was unaffected after 15 min superfusion with any one of the following agents: L-NOARG (0.1 mM). L-NAME (0.1 mM), L-arg (10 mM). 4. ACh (0.03 mM, 0.1 mM and 0.3 mM) elicited a significant increase of microvascular blood flow (171 +/- 16%, 214 +/- 55%, and 323 +/- 68% of baseline values, respectively), via interaction with the muscarinic receptor, for the vasodilator response was severely inhibited by 15 min superfusion with atropine (0.3 mM). 5. Following 15 min superfusion with either of the L-arg analogues (0.1 mM), the ACh-induced vasodilator response was significantly inhibited. Pretreatment with L-arg (10 mM) for 5 min, followed by co-administration of L-arg (10 mM) and L-NOARG (0.1 mM) for another 15 min significantly prevented the inhibitory effect of L-NOARG or ACh-induced vasodilatation. However, a similar pretreatment schedule with L-arg failed to prevent L-NAME from exerting its inhibitory effect. 6. Neither of the L-arg analogues potentiated sodium nitroprusside (10 microM and 30 microM)-induced vasodilatation. However, adenosine (0.1 mM)-induced vasodilatation was slightly but significantly attenuated by either L-NOARG (0.1 mM) or L-NAME (0.1 mM), an effect which was prevented by L-arg (10 mM). 7. In conclusion, an increase in endothelium-dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that L-NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that L-NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.

The effects of glibenclamide (GLB), a specific blocker of ATP-sensitive potassium (KATP) channels, and tetraethylammonium (TEA) on modulating the regulation of diaphragmatic microcirculation were assessed in anesthetized mechanically ventilated rats. With bicarbonate-buffered Ringer solution continuously suffusing the left hemidiaphragm, microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Hemorrhagic hypotension (HH) was induced via bleeding into a pressure reservoir. Five sets of experiments were performed. In set 1 (n = 6), the vasodilator effect of diazoxide (3 x 10(-4) M) was abolished after a 30-min suffusion with GLB, whereas the vasodilator effect of sodium nitroprusside (3 x 10(-6) M) remained the same. In set 2 (vehicle + HH; n = 23), a stepwise reduction in systemic arterial blood pressure (ABP) induced two distinct patterns of microvascular responses. Regulation of QLDF could be observed in pattern A animals in a range of ABP from 113 to 52 mmHg, whereas QLDF in pattern B animals rose progressively with declining ABP. In set 3 (GLB + HH; n = 17), baseline values of QLDF were not significantly affected after a 30-min suffusion of GLB (10(-5) M). During HH, two microvascular patterns similar to those in set 2 were observed. GLB significantly potentiated the reduction in QLDF in pattern A animals. In contrast, GLB had no effect on QLDF in pattern B animals. In set 4 (TEA + HH; n = 17), similar microvascular responses, compared with the vehicle group, were observed during HH after a 30-min suffusion of TEA (2 x 10(-3) M). In set 5 (n = 5), baseline values of QLDF were not significantly altered during sham hypotension. We conclude that 1) KATP channels are functional but not active in the resting diaphragmatic microcirculation and 2) KATP channels can modulate regulation of the microcirculation in the resting diaphragm during HH.

The aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs, divided into three groups. The animals were pre-treated with indomethacin (3 mg kg-1, i.v.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 i.v.) was administered as a bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused with sodium nitroprusside (SNP, 0.023 mg kg-1, i.v.), a donor of NO. Group 3 pigs (n = 3) were used as the controls. We evaluated diaphragmatic strength by measuring the transdiaphragmatic pressure (P di) generated during bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30s stimulation at 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak force between single twitches performed before and after the 30 s stimulation west. We also evaluated mean systemic (MAP) and pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (PW), systemic (SVR) and pulmonary vascular resistance (PVR) and cardiac output (CO). L-NAME increased MAP, MPAP, PW, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, PW and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was not significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR and the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attributed to a direct action of NO on skeletal muscle.

The purpose of this study was to determine the effect of inhibition of nitric oxide (NO) release on the diaphragmatic microvascular responses to hypoxia. In alpha-chloralose-anesthetized mongrel dogs, the microcirculation of the vascularly isolated ex vivo left hemidiaphragm was studied by intravital microscopy. The diaphragm was pump perfused with blood diverted from the femoral artery through a series of membrane oxygenators. The responses to supramaximal concentrations of sodium nitroprusside, moderate hypoxia (phrenic venous PO2 27 Torr), and severe hypoxia (phrenic venous PO2 15 Torr) were recorded before and after an infusion of NG-nitro-L-arginine (L-NNA; 6 x 10(-4) M) into the phrenic circulation for 20 min. Under control conditions, diaphragmatic blood flow was 12.4 +/- 1.1 ml.min-1.100g-1. Diaphragmatic blood flows recorded during moderate and severe hypoxia were 15.6 +/- 1.2 and 24.3 +/- 1.5 ml.min-1. 100 g-1, respectively (P < 0.05 for both compared with control values). Treatment with L-NNA reduced diaphragmatic blood flow to 9.6 +/- 0.8 ml.min-1.100 g-1 under control conditions (P < 0.05) and caused arteriolar vasoconstriction to a degree that was dependent on vessel size (i.e., larger vessels constricted more than smaller vessels). L-NNA eliminated the increase in blood flow during moderate hypoxia and inhibited arteriolar dilation by an amount that was related to vessel size (i.e., dilation of larger vessels was inhibited more than that of smaller vessels). Inhibition of NO synthesis had no effect on the increase in diaphragmatic blood flow (23.6 +/- 1.9 ml.min-1.100 g-1; P > 0.05 compared with that during severe hypoxia before treatment with L-NNA) or arteriolar diameters during severe hypoxia. NO release plays a role in the diaphragmatic vascular response to hypoxia, but this role is limited to dilation of larger arterioles during hypoxia of moderate severity.

The ventilatory muscles perform various functions such as ventilation of the lungs, postural stabilization, and expulsive maneuvers (e.g., coughing). They are classified in functional terms as inspiratory muscles, which include the diaphragm, parasternal intercostal, external intercostal, scalene, and sternocleidomastoid muscles; and expiratory muscles, which include the abdominal muscles, internal intercostal, and triangularis sterni. The ventilatory muscles require high-energy phosphate compounds such as ATP to fuel the biochemical and physical processes of contraction and relaxation. Maintaining adequate intracellular concentrations of these compounds depends on adequate intracellular substrate levels and delivery of these substrates by arterial blood flow. In addition to the delivery of substrates, blood flow influences muscle function through the removal of metabolic by-products, which, if accumulated, could exert negative effects on several excitatory and contractile processes. Skeletal muscle substrate utilization is also dependent on the ability to extract substrates from arterial blood, which, in turn, is accomplished by increasing the total number of perfused capillaries. It follows that matching perfusion to metabolic demands is critical for the maintenance of normal muscle contractile function. In this article, I review the factors that influence ventilatory muscle blood flow. Major emphasis is placed on the diaphragm because a large number of published reports deal with diaphragmatic blood flow. The second reason for focusing on the diaphragm is because it is the largest and most important inspiratory muscle.

The effects of anaesthetics on the microcirculation of the diaphragm are incompletely understood. Therefore, we assessed by in vivo intravital microscopy in rats the action of halothane on diaphragmatic arteriolar diameter and the role of nitric oxide and prostaglandins on halothane-induced diaphragmatic arteriolar diameter. We studied 54 rats anaesthetized with thiopentone. Dose-response curves to topically applied Krebs' solution saturated with halothane at increasing concentrations of 0%, 1%, 3% and 5% were carried out in the presence of an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNA), 300 mumol litre-1) or inhibitors of prostaglandin synthesis (mefenamic acid 20 mumol litre-1 or indomethacin 20 mol litre-1) or in the absence of any inhibitor. We found dose-dependent arteriolar dilatation which was abolished by mefenamic acid and indomethacin. In contrast, the effect of halothane was not modified by LNA. These data demonstrated that halothane-induced arteriolar dilatation in the diaphragm of the rat was mediated by prostaglandins but not by nitric oxide.

We report a case of life-threatening hemothorax three months after surgical repair of pectus excavatum. Angiography revealed the hemorrhage to originate from a laceration of the phrenic artery secondary to dislodgment of the metal strut used for the repair. Awareness of this rare complication in patients after repair of pectus excavatum is required.

The phrenic artery is a small vessel that is not often visualized on CT and is at risk of injury during biopsy of low lung lesions. This may result in haemoperitoneum that will not be evident on post-biopsy chest X-rays. We present a patient with a bleeding tendency who had this unusual complication following a needle aspiration lung biopsy.

Purpose: In the vascularly isolated canine hemidiaphragm, we tested the hypothesis that alpha-adrenoreceptor stimulation may influence diaphragmatic function and O2 extraction during reductions in O2 delivery (QO2di)., Methods: The diaphragm was perfused using a constant flow pump with blood diverted from the left femoral artery. QO2di was reduced in a stepwise fashion by progressive reductions in pump flow. The tension generated by the contracting diaphragm (3 Hz), the critical O2 delivery (QO2di,c) below which O2 consumption (VO2di) becomes dependent on O2 supply and the oxygen extraction ratio at this critical point (ERc) were assessed in two groups of animals. Phenylephrine (10(-5) mol/L) was infused into the phrenic artery in one group and saline was infused in another group., Results: In the contracting diaphragm, VO2di was higher in the phenylephrine infused group than in the control group (5.2 +/- 0.5 vs 2.11 +/- 0.3 mL/min/100 g). QO2di,c and ERc were also higher in the phenylephrine group than in the control group (6.16 +/- 0.43 vs 3.1 +/- 0.5 mL/min/100 g and 0.87 +/- 0.035 vs 0.63 +/- 0.05, respectively). In the resting diaphragm, VO2di was not significantly different between the two groups and no critical oxygen delivery could be identified in either group., Conclusions: These results indicate that alpha-adrenoreceptor activation may increase the tension generated by the diaphragm as well as its oxygen consumption and oxygen extraction. Although this may be beneficial during moderate reductions in oxygen delivery, in more severe shock states, activation of these receptors by endogenous or exogenously administered catecholamines may hasten the development of delivery limitation of VO2di and compromise the ability to sustain ventilation.

Purpose: The purpose of this study was to determine the effect of increasing the concentrations of sevoflurane anaesthesia on the distribution of diaphragm blood flow (Qdi) in ten dogs during mechanical ventilation., Methods: Animals were divided into two groups, sevoflurane (n = 6) and time control (n = 4) groups. Blood flow to the crural and the costal diaphragm (Qcru, Qcost) was determined by the hydrogen clearance technique at 0, 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC) of sevoflurane after a 30 min period of steady-state conditions. Cardiac output (CO) and the mean arterial blood pressure (MBP) were also measured., Results: Sevoflurane anaesthesia caused a reduction in CO (L.min-1) from a control value of 1.51 +/- 0.21 to 1.38 +/- 0.1 (0.5 MAC), 1.09 +/- 0.15 (1.0 MAC) and 0.98 +/- 0.12 (1.5 MAC) (Mean +/- SD). Mean blood pressure, Qcru and Qcost also decreased with increasing depth of anaesthesia. In addition, the decrease of Qcru was greater than that of Qcost at all levels of MBP and CO. No change occurred in these variables in the time control group., Conclusion: Sevoflurane anaesthesia changes the distribution of Qdi with a greater reduction occurring in Qcru than in Qcost.

Phosphorescence quenching techniques measure microvascular PO2 without direct surgical manipulation of the tissue. At a given arterial PO2, microvascular PO2 reflects the local O2 uptake-to-O2 delivery ratio, i.e., VO2/QO2. We evaluated the potential of phosphorescence quenching to determine microvascular PO2 in the rat costal diaphragm (PdiaO2). PdiaO2 and arterial blood gases were monitored across transient changes of inspired O2 among 21, 10, and 100% and also during hypotensive states evoked by progressive phlebotomy. After a transit delay, PdiaO2 responded rapidly to alterations of inspired and thus arterial PO2, with half times of the response averaging 5-7 s for switches to a lower inspired O2 (i.e., from 21 to 10%, from 100 to 21%, and from 100 to 10%) and also from 10 to 21%. By comparison, half times of the 10 to 100% and 21 to 100% switches were longer [11 s (P = 0.085) and 21 s (P < 0.05), respectively]. Below a mean arterial blood pressure (BP) of 120-130 mmHg, PdiaO2 decreased as a linear function of BP, with these variables being significantly correlated in each instance (n = 5, r = 0.851-0.937, P < 0.01 for all animals). From these results, it appears feasible to measure PdiaO2 in the spontaneously breathing rat in vivo under steady-state and transient conditions. Also, during progressive hypotension, the fall in PdiaO2 is significantly related to falling BP, likely as a consequence of an increased metabolic demand (increased ventilation and diaphragm VO2) concomitant with decreased blood flow. We conclude that phosphorescence quenching techniques offer a powerful tool for assessing diaphragm physiology and pathophysiology.

To gain insight into diaphragm functional heterogeneity, blood flow (expressed as ml.min-1 x 100 g-1) was measured using radiolabeled microspheres in the ventral, medial, and dorsal regions of the costal diaphragm and in the crural diaphragm of sedentary control (S) and exercise trained (ET) female Wistar-Kyoto rats at rest and during treadmill exercise. ET animals had performed moderate intensity exercise training on a motorized treadmill (22 m/min, 10% grade, 60 min/d) for 12 months, while S were cage-confined. The efficacy of exercise training was demonstrated by a 12% increase (P < 0.05) in ventricular weight-to-body weight ratio and increases (P < 0.05) in citrate synthase activity in hindlimb skeletal muscles of ET. At rest, blood flow in the ventral costal diaphragm (16 +/- 1) averaged approximately 61% of that in the medial (26 +/- 3) and dorsal (25 +/- 2) costal regions (P = 0.035), and crural diaphragm flow was 23 +/- 3. During treadmill exercise (5 min at 22 m/min, 10% incline), blood flow increased an average of 5-fold (P < 0.001) throughout the diaphragm, but the heterogeneous flow pattern persisted; i.e., blood flow remained lower (P = 0.003) in the ventral region (77 +/- 7) than either the medial (135 +/- 15) or dorsal (127 +/- 11) costal regions. Flow in the crural diaphragm during exercise was intermediate (105 +/- 9). Exercise training did not alter either the magnitude of blood flows or the flow distribution pattern within the diaphragm. Citrate synthase activity was two-fold that of the plantaris muscle and was uniform across the ventral, medial, and dorsal costal and the crural diaphragm of a second group of age-matched rats (P = 0.57). These data demonstrate that, although oxidative capacity is uniform throughout the diaphragm, there is a significant regional heterogeneity of blood flow within the rat diaphragm both at rest and during locomotory exercise. The greater flow in the medial and dorsal regions of the costal diaphragm suggests that these regions sustain a greater portion of the inspiratory work load at rest and during exercise compared to the ventral region.

We assessed the role of nitric oxide (NO) in the regulation of diaphragmatic O2 uptake (Vo2di) and phrenic vascular resistance during endotoxemia in anesthetized, mechanically ventilated dogs. Left diaphragmatic vasculature was isolated and briefly pump perfused with arterial blood at a normal flow rate, at a high rate (50% higher than normal), and at low rat (60 to 70% lower than normal). At each rate, Vo2di and phrenic perfusion pressure (Pphr) were measured. Escherichia coli endotoxin (100 mg) was infused intravenously over 90 min in several groups of animals, whereas normal saline was infused into the other. Endotoxin infusion increased Vo2di and reduced Pphr at a given flow rate. These parameters remained unchanged in the saline-infused animals. Infusion of NG-nitro-L-arginine methyl ester (LNAME 6 x 10(-4) M) into the phrenic artery of the endotoxin group reversed the decline in Pphr with no effect on Vo2di. LNAME infusion in the saline group increased Pphr at normal and high flow rates only. Single intravenous injections of LNAME increased arterial pressure and reduced cardiac output in endotoxemic animals, whereas only an increase in arterial pressure was observed in saline-infused animals. Serum arterial and phrenic venous NO concentrations measured in separate groups of animals increased significantly after endotoxin infusion, whereas saline infusion had no effect on these parameters. These results indicate that enhanced NO release plays a significant role in endotoxin-induced phrenic and systemic vasodilation. However, the increase in Vo2di in the endotoxin group does not seem to be mediated by NO release.

Purpose: To determine the prevalence and appearance of cardiophrenic angle (CPA) varices at computed tomography (CT) in patients with portal hypertension (PHT)., Materials and Methods: A retrospective review was performed of 148 consecutive contrast material--enhanced abdominal CT scans of patients with PHT. The paracardiac region was assessed for tubular structures suggestive of varices. Variceal diameter and CT attenuation relative to adjacent liver were noted., Results: Tubular structures consistent with CPA varices were noted in 29 cases and were more common on the right side than on the left. Mean CPA variceal diameter was 2.6 mm. In three cases, right CPA varices measured 10-13 mm in diameter, but no variceal enhancement was noted on initial dynamic CT images. Delayed CT demonstrated contrast enhancement that reflected delayed enhancement of the portal venous system., Conclusion: CPA varices, particularly on the right side, are not uncommon in patients with PHT. Varices should be considered and excluded as a cause of CPA masses, particularly before percutaneous biopsy. Delayed CT may be necessary to correctly delineate CPA varices.

The applicability of laser-Doppler flowmetry (LDF) in measuring regional blood flow of the diaphragm (Qdi) was evaluated in anesthetized and mechanically ventilated rats. Specifically, we assessed the issues of the degree of tissue perfusion, spatial variations of Qdi signals, and the correlation between these signals and total Qdi. Qdi was detected from an area 1 mm in diameter and 0.5 mm in depth. With Ringer solution continuously suffusing the abdominal surface of the left hemidiaphragm, drugs were applied to the surface of the diaphragm at 1/100 of the flow rate of the suffusing fluid. In 13 rats, resting Qdi and the response of Qdi to a single concentration of adenosine (10(-4) M) remained unchanged over a 2-h period. Increasing adenosine concentrations (10(-9) to 10(-3) M) in eight rats elicited a progressive rise in Qdi. In six rats, the variability of Qdi in a given rat was assessed over five different sites at 2-mm intervals in a line on the diaphragm. A wide range of variability in Qdi was noticed among different sites. The depth of tissue penetration of LDF was little affected when a piece of freshly diaphragm was interposed between the probe and the perfused diaphragm, suggesting that LDF signals arise from complete penetration of the perfused diaphragm. Finally, significant linear relationships between mean Qdi and total Qdi were observed in all animals; however, the slopes of these relationships varied significantly between animals. In conclusion, LDF provides a stable and continuous method for monitoring regional microvascular diaphragmatic perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of theophylline on diaphragmatic blood flow (Qdi) and oxygen consumption (VO2di) was studied in eight lightly anesthetized dogs during quiet breathing and inspiratory resistive loading. Qdi was determined with the radioactive microsphere tracer technique, and VO2di was calculated as the product of Qdi and the diaphragmatic arterio-venous oxygen difference. During quiet breathing, theophylline increased minute ventilation (9.3 +/- 1.7 versus 5.1 +/- 0.4 L/min), mean inspiratory flow (547 +/- 60 versus 378 +/- 56 ml/s), and duty cycle (0.270 +/- 0.042 versus 0.192 +/- 0.024) but did not significantly alter Qdi or VO2di. Conversely, Qdi increased significantly during loaded breathing compared with quiet breathing (37 +/- 4 versus 27 +/- 3 ml/100 g/min) and was further increased by theophylline (45 +/- 7 ml/100 g/min). Theophylline did not alter the tension-time index of the diaphragm (TTdi) during inspiratory resistive loading (0.054 +/- 0.006 versus 0.056 +/- 0.004, p NS) but resulted in a disproportionate and significant increase in VO2di (2.66 +/- 0.53 versus 1.78 +/- 0.26 ml/100 g/min). Similarly, total-body oxygen consumption (VO2TB) during inspiratory loading increased significantly after theophylline (24%), but the tension-time index of the inspiratory muscles (TTi), a measure of the total respiratory load, was unchanged. We conclude that theophylline significantly increases VO2di and VO2TB at the same TTdi and TTi during resistive loading. This enhanced energy expenditure needs consideration in the clinical management of pulmonary disorders that increase the work of breathing.

Group B Streptococcus (GBS) causes an impairment of diaphragmatic pressure generation (Pdi) in 2-wk-old piglets, whereas 4-wk-old piglets are unaffected. In this study, we examined the effect on 4-wk-old piglets of a higher dose of GBS than previously utilized. We sought to determine whether an eicosanoid product of arachidonic acid metabolism accounted for the decrease in Pdi during GBS infusion and whether thromboxane A2 (TxA2) is the putative eicosanoid mediator of decreased Pdi during GBS infusion. Measuring Pdi during phrenic nerve stimulation, we studied four groups of anesthetized spontaneously breathing 4-wk-old piglets. Group 1 (GBS) was infused with live GBS, which caused a decrease in Pdi by 1 h at 20-, 30-, 50-, and 100-Hz stimulation frequencies. Group 2 [GBS + indomethacin (Indo)] was pretreated with Indo before GBS infusion. In the GBS + Indo group, Pdi did not decrease throughout 4 h of GBS infusion. Because Indo proved to be protective of Pdi during GBS infusion, we examined the role of TxA2, the only eicosanoid present at 1 h in the serum of GBS-infused piglets. Group 3 was infused with the TxA2 analogue U-46619 only for 1 h. Group 4 was treated with the TxA2-receptor antagonist SQ-29548 before and concomitant with GBS infusion for 1 h; the SQ-29548 was then discontinued, and GBS was continued for 1 h more. In the U-46619-infused group, Pdi decreased at 1 h, and in the SQ-29548-treated group, Pdi did not decrease during GBS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

In the accompanying papers, we demonstrated that two murine ascites tumors (MOT and TA3/St) induced peritoneal lining blood vessels to become hyperpermeable to plasma proteins, leading to extravasation of fibrinogen and its clotting to cross-linked fibrin in peritoneal lining tissues (peritoneal wall, mesentery, and diaphragm). In solid tumors, vascular hyperpermeability and fibrin deposition lead to the generation of vascularized connective tissue. In order to determine whether fibrin had similar consequences in ascites tumors, the vasculature and stroma of peritoneal lining tissues were analyzed at successive intervals after i.p. tumor cell injection. In both MOT and TA3/St ascites tumors, the size and number of peritoneal lining microvessels increased significantly by 5-8 days. Subsequently, peritoneal lining vessels increased in cross-sectional area by as much as 15-fold and peritoneal vascular frequency increased by up to 11-fold. Incorporation of [3H]thymidine by mesenteric blood vessels was negligible in control animals but came to involve 20 and 40% of endothelial cells lining mesenteric vessels in MOT and TA3/St ascites tumor-bearing mice, respectively. After an early dramatic increase in cross-sectional area, peritoneal lining microvessels subsequently underwent a novel form of remodeling to smaller average size as the result of transvascular bridging by endothelial cell cytoplasmic processes. Thus, both of the ascites tumors studied here induced angiogenesis and stroma similar to that elicited when these same tumors were grown in solid form. However, stroma developed more slowly in ascites than in solid tumors and was entirely confined to a compartment (peritoneal lining tissues) that was distinct from that (peritoneal cavity) containing the majority of tumor cells and ascites fluid. These findings are consistent with the hypothesis that vascular hyperpermeability, induced in both solid and ascites tumors by tumor cell-secreted vascular permeability factor, is a common early step in tumor angiogenesis, resulting in fibrinogen extravasation, fibrin deposition, and likely other alterations of the extracellular matrix that together stimulate new vessel and fibroblast ingrowth.

The authors are reporting an exceptional case of unexpected venous anastomosis between a right inferior diaphragmatic venous and a right hepatic venous discovered during a total hepatectomy before an orthotopic transplantation. Never described in the literature, this abnormality may be explained by the embryology of the transversum septum, junction of the hepatic draft and the draining tracts of the future diaphragm.

In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, we studied the effect of intra-arterial infusion of the nitric oxide (NO) inhibitor NG-nitro-L-arginine (LNA) on the relationship between phrenic arterial perfusion pressure (Pphr) and blood flow (Qphr). In separate groups of animals, either saline or LNA (final concn 6 x 10(-4) M) was infused into the phrenic artery over 20 min. The diaphragm was then autoperfused by diverting flow from the left femoral artery. Arterial blood pressure was reduced in stages by controlled hemorrhage. The Pphr-to-Qphr relationship was plotted for each animal, and the third-order polynomial of best fit was determined by least squares regression. The inflection point of this relationship was determined for each animal. In the contracting and resting diaphragms, the inflection point corresponded to Pphr values of 83.6 +/- 4.7 and 72.5 +/- 6.8 mmHg, respectively, in the saline-treated group compared with 86.2 +/- 2.7 and 76.8 +/- 5.1 mmHg, respectively, in the LNA-treated group. In the contracting diaphragm, LNA reduced Qphr uniformly across the entire range of perfusion pressures. In the resting diaphragm, the effect of LNA was not uniform. At perfusion pressures below the inflection point, the flow was reduced in proportion to the reduction in inflection point flow. At higher perfusion pressures, Qphr was decreased to a greater extent than could be accounted for by the change in inflection point flow.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the effect of endothelium-derived relaxing factor (EDRF) on the diaphragmatic microcirculation under basal conditions and after vasodilator stimulation, prepared diaphragms from anesthetized rats were studied. With bicarbonate-buffered Ringer's solution suffusing the diaphragm, the microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Drugs were applied to the surface of the diaphragm. Five series of experiments were performed. In Series 1, the effects of acetylcholine (ACh, 10(-4) M) and sodium nitroprusside (SNP, 3 x 10(-6) M) were measured before and after 15 minutes suffusion of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Trend analyses revealed that the vasodilator effect of SNP was not affected, while that of ACh was abolished by L-NAME. In Series 2, both ACh and SNP elicited a concentration-dependent increase in QLDF. In Series 3, following 15 minutes suffusion with L-NAME (10(-4) M), there was no change in baseline QLDF and the ACh-induced QLDF change was abolished, while the effect of SNP was maintained. In Series 4, five minutes of pretreatment with L-arginine (L-arg, 10(-2) M), followed by co-administration of L-arg (10(-2) M) and L-NAME (10(-4) M) for another 15 minutes, did not prevent the inhibitory effect on ACh-induced QLDF change by L-NAME. In Series 5, 20 minutes application of L-arg (10(-2) M) alone did not affect baseline QLDF. Also, L-arg did not influence the ACh-induced vasodilating response, whereas it slightly increased the SNP-induced vasodilating response.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated by intravital microscopy in rats the relative importance of nitric oxide (NO) and prostaglandins in 1) the maintenance of basal diaphragmatic arteriolar tone and 2) the response of diaphragmatic arterioles to the endothelium-dependent vasodilator acetylcholine (ACh). One hundred two mechanically ventilated rats were studied. Separate applications of N omega-nitro-L-arginine (L-NNA) and mefenamic acid (MA), which are specific inhibitors of NO and prostaglandin synthesis, respectively, elicited a significant reduction in basal diaphragmatic arteriolar diameter. A dramatic potentiation of the effect of each inhibitor was observed when both agents were applied simultaneously. ACh application induced a significant and dose-dependent increase in arteriolar diameter that was not significantly modified by the separate application of L-NNA or MA. Conversely, the simultaneous administration of L-NNA and MA almost completely prevented ACh-induced arteriolar dilatation. Dilatation in response to sodium nitroprusside was not significantly modified in the presence of both inhibitors. These results suggest that NO and prostaglandins act in concert to regulate basal diaphragmatic arteriolar tone and to mediate diaphragmatic arteriolar response to ACh.

When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically.

The goal of this study was to determine whether in the dog ATP-sensitive K+ channels blocked with glibenclamide affect diaphragmatic blood flow [phrenic arterial blood flow (Qpa)] during both spontaneous breathing at rest and increased diaphragmatic activity. A control group (no glibenclamide; n = 4) and an experimental group (50 mg/kg of glibenclamide; n = 5) were studied. During spontaneous breathing at rest, Qpa was 15.0 ml.min-1 x 100 g-1 and decreased by 5% in the presence of glibenclamide. Diaphragmatic pacing (30 min-1) generated by phrenic nerve pacing produced an initial diaphragmatic tension-time index of 0.25 in both groups. A 50% decay in transdiaphragmatic pressure was reached at 165 s in the experimental group compared with 421 s in the control group. Diaphragmatic pacing increased Qpa by 46% in the experimental group and 65% in the control group, yielding a 63% greater vascular resistance in the experimental group. Phrenic vein K+ content at rest was unchanged by the presence of glibenclamide, being 3.6 +/- 0.16 mmol/l compared with 3.5 +/- 0.19 mmol/l in the control group. Phrenic nerve pacing in the control group produced a 13% increase in phrenic vein K+ content, whereas in the experimental group a 16% decrease was observed. We suggest that ATP-sensitive K+ channels play an important role in the modulation of Qpa.

We measured blood flow to the respiratory muscles of the fetal lamb using the radioactively-labelled microsphere technique in order to assess whether fetal breathing is an energetically costly activity as has been reported. Diaphragm flow ranged from 6.4-35.2 ml.min-1.100 g-1 during fetal apnoea and rose to 21.1-615 ml.min-1.100 g-1 during fetal breathing (P < 0.02; n = 7). Parasternal muscle flow also increased significantly (P < 0.02) between fetal apnoea and breathing while external and internal intercostal flows did not change. Expressed as a percentage of cardiac output the diaphragm received 0.08-0.28% during apnoea and 0.22-2.2% during fetal breathing. Neither placental blood flow nor fetal O2 consumption increased significantly between fetal apnoea and breathing. We conclude that the levels of perfusion required by the respiratory muscles for breathing in the fetus are inconsistent with fetal breathing costing a large proportion of the fetal O2 budget.

Purpose: In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, the hypothesis that nitric oxide (NO) is an important regulator of diaphragmatic O2 extraction was tested., Methods: The effect of an intra-arterial infusion of an NO-synthase inhibitor NG-nitro-L-arginine (L-NA) on the critical O2 delivery (QO2c), below which O2 consumption becomes dependent on O2 supply, was assessed in two groups of animals in which either saline or L-NA (6 x 10(-4) mol/L) was infused into the phrenic artery over 20 minutes. The diaphragm was then perfused either by left femoral arterial blood (autoperfusion) or by pump perfusion with blood from the femoral artery. QO2 was reduced by stepwise hemorrhage in the autoperfusion groups and by reducing the pump rate in the pump perfusion groups., Results: During autoperfusion, QO2c in the saline- and L-NA-treated groups was not different (0.88 +/- 0.15 and 0.98 +/- 0.12 mL/min/100 g, respectively) for the resting diaphragm. Critical O2 extraction ratios were not different (64.5% +/- 9.9% and 67.8% +/- 6.4%, respectively). In the saline group, QO2c during 3-Hz stimulation was 5.03 +/- 0.9 mL/min/100 g. In the L-NA group, diaphragm flow was lower than the saline group, and no QO2c was found. In the pump-perfused contracting diaphragm, QO2c in both groups did not differ (3.1 +/- 0.5 and 4.05 +/- 0.65 mL/min/100 g, respectively). O2 extraction ratios at these O2 deliveries were different (63.3% +/- 5.2% and 77.4% +/- 4.3%, respectively). However, NO-synthase inhibiton had no effect on maximum diaphragmatic O2 extraction ratio., Conclusions: These results indicate that NO release is an important modulator of the tone of diaphragmatic resistance vessels, but it does not appear to regulate the processes by which O2 extraction is enhanced to compensate for decreased O2 delivery.

1. The role played by nitric oxide (NO) in the regulation of blood flow to the canine isolated hemidiaphragm was evaluated by determining (a) the effects of the L-arginine analogues NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-L-arginine (L-NOARG), and argininosuccinic acid (ArgSA) on baseline vascular resistance and of the latter two agents on endothelium-dependent (acetylcholine, ACh) and endothelium independent (sodium nitroprusside, SNP) vasodilatation; (b) the effects of L- and D-arginine on baseline vascular resistance; and (c) the effects of L-glutamine, an inhibitor of intracellular recycling of L-citrulline to L-arginine, on baseline resistance and on the response to ACh and SNP. 2. L-NAME, L-NOARG and ArgSA (6 x 10(-4) M final concentration) increased baseline diaphragmatic vascular resistance to a similar extent (28.6 +/- 4.2%, 26.7 +/- 4.3% and 32.8 +/- 4.6% respectively). L-NOARG and ArgSA reversed the vasodilator effect of ACh but not of SNP. 3. L- and D-arginine had no effect on vascular resistance. 4. L-Glutamine (10(-3) M) increased baseline vascular resistance by 10 +/- 1.9% (P < 0.05) but did not alter responses to either ACh or SNP. 5. Basal NO release plays a role in the regulation of baseline diaphragmatic vascular resistance. L-Arginine analogues tested potently and specifically inhibited this process. Moreover, extracellular L-arginine appears to have no effect on baseline diaphragmatic vascular resistance.

Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, large-conductance, and small-conductance Ca(2+)-activated K+ channels, respectively) were infused into the diaphragmatic vasculature of anesthetized indomethacin-treated dogs to assess the contribution of K+ channels to active hyperemia. Diaphragmatic blood flow (Qphr) and O2 uptake (VO2di) were measured at rest and during 2 min of continuous left phrenic nerve stimulation at 0.5, 1, 2, and 4 Hz. These measurements were repeated before (control) and after the infusion of a selective K+ channel blocker in three groups of animals. Glibenclamide at 10(-5) M significantly attenuated Qphr at rest and in response to all stimulation frequencies. Whereas resting VO2di remained unchanged, glibenclamide infusion significantly reduced VO2di in response to all stimulation frequencies. The slope of the linear relationship between Qphr and VO2di, however, was not affected by glibenclamide. By comparison, infusion of iberiotoxin (10(-7) M) in a second group reduced Qphr at rest and in response to 0.5- and 1-Hz stimulation, whereas Qphr measured in response to 2- and 4-Hz stimulation remained similar to control values. Apamin (10(-6) M) infusion in a third group reduced only resting Qphr with no effect on active hyperemia during phrenic nerve stimulation. Neither iberiotoxin nor apamin influenced resting or stimulated VO2di. In all groups diaphragmatic tension measured after the infusion of K+ channel blockers remained similar to control values. These results indicate that K+ channels, especially those sensitive to glibenclamide, modulate the increase in Qphr and VO2di in response to moderate augmentation of metabolic demands.

The exercise blood flow response of muscles involved in respiration was determined in rats with a myocardial infarction (MI), which was produced by tying the left main coronary artery, and in rats that underwent sham operations (Sham). Arterial blood gases, acid-base parameters, and blood flow (ml/100 g of tissue) to the diaphragm, intercostals, and transverse abdominis muscles were measured during steady-state treadmill exercise (20% grade, 28 m/min). The responses of MI rats that were classified as having a small (MIS < 25%, n = 7), medium (25% < or = MIM < or = 35%, n = 8), and large (MIL > 35%, n = 7) infarct were compared with those of Sham (n = 12) rats using analysis of variance techniques. Results demonstrated that arterial PO2 and PCO2 were similar for all groups during exercise (PaO2 = 110-112 mmHg; PaCO2 = 28-29 mmHg) even though the MIM and MIL groups had developed a significant amount of pulmonary congestion, and the MIL group demonstrated indicators of severe left ventricular dysfunction. Blood flow to the diaphragm during exercise was significantly greater for the MIL group of rats, although blood flow to the intercostals and transverse abdominis muscles was similar across the different groups. Results from this study support the contention that MI rats (including rats with decompensated heart failure) will achieve the same effective alveolar ventilation during exercise as that found for Sham rats and in the process maintain arterial O2 saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to measure certain cardiovascular effects of 2 or 11 micrograms nifedipine/kg body weight given intravenously to dogs anesthetized with fentanyl-droperidol-pentobarbital. Parameters measured were: cardiac output, stroke volume, stroke work, systemic arterial pressure and vascular resistance, splenic weight (a measure of venous capacitance), and fractionation of cardiac output to many tissues. In response to doses of nifedipine, systemic vascular resistance decreased, cardiac output and flows to most organs increased, and heart rate, stroke work, and splenic capacitance were unchanged. The flow to the diaphragm increased more than that to other organs.

In the capillary physiology literature, molecules and particles larger than 10 nm are assumed to leave the plasma mostly through large pores located at the level of intercellular junctions in microvessels lined with a continuous endothelium. In morphological studies of similar microvessels, outgoing particles > 10 nm were detected in endothelial plasmalemmal vesicles not in intercellular junctions. Because the probes may not be found in transit through the junctions because they may be swept away by strong currents generated by Starling forces, we have examined a large number of junctions in arteriolar, capillary, and venular segments of bipolar vascular fields of mouse diaphragms collected after perfusion with large pore probes. The results presented in this study indicate that 1) the perfused probes accumulate in the luminal introits of the junctions as filtration residues that decrease in size and frequency from arterioles to venules, and 2) large pore probes move across the endothelium exclusively through plasmalemmal vesicles.

A 21-year-old male developed pericardial tamponade in a delayed fashion after blunt chest trauma. Tamponade was not suspected clinically and was first seen on computed tomography of the abdomen. Plain films of the chest revealed distortion of the path of a Swan-Ganz catheter due to the ventricular compression. After drainage, left inferior phrenic artery embolization was performed to treat the persistent hemothorax.

Using alpha-chloralose-anesthetized mechanically ventilated vagotomized dogs, we assessed the effects of selective diaphragmatic paralysis on the inspiratory motor drive. Diaphragmatic paralysis was accomplished by a bolus injection of vecuronium, a neuromuscular junction blocker, into the left phrenic artery of an in situ vascularly isolated and innervated left diaphragm. The inspiratory motor drive during spontaneous breathing attempts was assessed by measuring peak integrated electromyographic (EMG) activities of the left and right diaphragms and parasternal and alae nasi muscles. Respiratory timing parameters were measured from the integrated EMG signals of the diaphragm. Three groups of dogs were studied. In group 1 (n = 9), vecuronium was injected into the phrenic artery with the left diaphragmatic length adjusted at the functional residual capacity. Vecuronium injection (0.2 mg) resulted in a significant decline in left diaphragmatic tension and integrated EMG. Breathing frequency increased by 24% of the baseline value, whereas right diaphragm, parasternal, and alae nasi EMG activities rose to 136, 227, and 165% of their respective baseline values a few seconds after the vecuronium injection. In group 2 (n = 6), vecuronium injection in left phrenectomized animals did not alter the EMG activities of the inspiratory muscles (left EMG signal was abolished) nor did it alter respiratory timing. In group 3 (n = 4), the left diaphragm was placed in a flaccid position. Vecuronium injection in this group did not produce any changes in the EMG activities or respiratory timing. We conclude that selective diaphragmatic paralysis elicits a significant rise in the inspiratory motor drive. This effect is likely to be mediated through the inhibition of diaphragmatic Golgi tendon organ activity.

Objective: Central linear densities are often seen at the level of the diaphragm on CT scans of the chest. To determine the cause of these densities, we evaluated helical CT scans and correlated the results with the findings from a study of cadavers., Subjects and Methods: Forty patients who had normal findings on conventional CT scans had helical CT of the entire chest. For the cadaveric study, we examined the lung bases and extrapleural spaces on the diaphragmatic surface in 22 formalinized cadavers., Results: On helical CT scans, linear densities extending laterally from the mid-part of the right side of the inferior vena cava and from the posterior margin of the left ventricle were seen on the right side of the chest in 12 subjects (30%) and on the left side in 17 subjects (42%). In the cadavers, the inferior phrenic artery and the accompanying vein ran over the diaphragmatic dome in the extrapleural space from the region of the inferior vena cava on the right and from the posterior margin of the left ventricle on the left. These supradiaphragmatic vessels were seen on the right side in 10 cadavers (45%) and on the left side in four cadavers (18%)., Conclusion: We conclude that these linear densities at the level of the diaphragm on CT scans of the chest represent the inferior phrenic artery and vein.

Radiolabeled (15-microns) microspheres were used to measure blood flow to upper airway muscles [alae nasi (AN), intrinsic laryngeal, tongue, cervical strap, and hyoid musculature], diaphragm (DI), and parasternals (PS) during spontaneous breathing in 24 anesthetized tracheotomized supine dogs. Six dogs were also studied while -28 +/- 3 (SE) cmH2O tracheal airway pressure was generated against an inspiratory resistance (IR) (upper airway bypassed). Blood flow to posterior cricoarytenoid muscle (PCA) [24.0 +/- 2.1 (SE) ml.min-1.100 g-1] was greater than that to DI (18.0 +/- 2.3 ml.min-1.100 g-1) and comparable to that to PS (21.4 +/- 2.9 ml.min-1.100 g-1). Blood flow per unit weight did not differ between AN, tongue muscles, laryngeal adductors, cervical strap muscles, and cricothyroid (CT). Average blood flow to these muscles was only 8.0 +/- 0.8 ml.min-1.100 g-1. With the exception of CT, blood flow to these upper airway muscles was less than that to DI and PCA. Relative to blood flow during spontaneous breathing, IR loading increased blood flow to AN by a factor of 7.5, to PCA by 3.4, to DI by 3.2 and to PS by 1.9. There was no change in blood flow in the other muscles during loading. Our results show that at rest blood flow to main glottic dilator (PCA) is similar to that to main inspiratory muscles. Furthermore, in response to an IR load, blood flow to PCA and AN increased by an equivalent or greater amount than that to DI.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effect of NG-nitro-L-arginine (L-NA) on reactive hyperemia in the vascularly isolated hemidiaphragm of anesthetized dogs pretreated with indomethacin. In nine animals, the diaphragm was autoperfused from the left femoral artery. Phrenic arterial flow was interrupted for 10-120 s during a control period and after 20 min of L-NA infusion (6 x 10(-4) M). Postocclusive flow and duration of hyperemia during the control period increased progressively with increasing occlusion duration. After L-NA infusion, baseline and postocclusive flow in response to all occlusions declined significantly compared with control values. However, when normalized as percentage of baseline flow, postocclusive flow remained similar to that during the control period. By comparison, the duration of reactive hyperemia was significantly shortened by L-NA infusion. In five animals, we repeated the same protocol during pump perfusion of the diaphragm at a fixed flow rate. L-NA infusion increased baseline and postocclusive phrenic resistance in response to all occlusion durations; however, postocclusive phrenic resistance as percentage of baseline remained similar to control values. In addition, hyperemia durations in response to 60- and 120-s occlusions were shortened significantly by L-NA infusion. We conclude that 1) endothelium-derived relaxing factor plays an important role in the regulation of baseline vasomotor tone in the diaphragm and 2) modulation of endothelium-derived relaxing factor release contributes to the reactive vasodilatory response to transient vascular occlusion in the diaphragm.

Hepatic venous outflow tract obstruction, Budd-Chiari syndrome (BCS), leads to portal hypertension and to the development of collaterals that bypass the obstruction. Described here is a BCS patient with an unusually large transdiaphragmatic collateral between the left hepatic and left innominate veins, which decompressed the oesophageal varices. This has not been reported earlier in the literature.

We assessed the role of groups III and IV phrenic afferents in the ventilatory response to diaphragmatic ischemia in mechanically ventilated, chloralose-anaesthetized dogs using the in-situ isolated and innervated left hemidiaphragm preparation. The inspiratory motor drive to the right (Rt Edi) and left (Lt Edi) diaphragms, parasternal (Eps), and alae nasi (Ean) muscles was measured from the peak integrated EMG activities. When left diaphragmatic ischemia was produced in the control group (n = 6) by occluding the left phrenic artery for 20 min, LtEdi increased to 158%, RtEdi to 160%, Eps to 150% and Ean to 135% of baseline values. Left diaphragmatic tension, however, remained unchanged during the ischemia period. In the capsaicin-treated group (n = 6), we injected repeated doses of capsaicin, a selective stimulant of groups III and IV afferents, into the left phrenic artery to eliminate inputs from these afferents. Repeated injections of capsaicin are known to induce prolonged periods of afferent dysfunction. The first two injections of capsaicin (1 mg each) produced transient activation of the inspiratory muscles and higher breathing frequencies. Subsequent injections, however, failed to elicit any ventilatory changes. When diaphragmatic ischemia was induced after the last injection of capsaicin, no changes in the Right Edi, Eps and Ean were observed, whereas Left Edi and left diaphragmatic tension declined significantly. We conclude that increased inspiratory motor drive during selective diaphragmatic ischemia is mediated through the activation of groups III and IV phrenic afferents.

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.