Laser revascularization of ischemic skeletal muscle.

BACKGROUND: Clinical trials have shown that transmyocardial laser revascularization is an effective secondary treatment for ischemic heart disease patients. Laser revascularization may also provide an alternative method for treating peripheral vascular disease. METHODS: The purpose of this study was to investigate the potential for laser revascularization in ischemic skeletal muscle. Eighteen rabbits (3-4 kg) were instrumented chronically with transit time ultrasound flowprobes on both common iliac arteries. All rabbits performed graded exercise tests on a treadmill where maximal blood flow was recorded. Unilateral hindlimb ischemia was produced by ligation of one femoral artery. At week 3 postligation, 10 rabbits received laser therapy and 8 underwent a sham surgery. In each of four muscles (gracilius, medialis, sartorius, and biceps femoris) 5 to 22 laser channels were created (average = 52 channels per leg). RESULTS: At week 3 postligation the maximal blood flow of the ischemic limb for the treated group was 64 +/- 3 ml/min (mean +/- SEM) and at 6 weeks postlaser therapy maximal blood flow increased to 75 +/- 5 ml/min. The sham surgery group had a maximal blood flow of 58 +/- 4 ml/min at week 3 postligation and 66 +/- 3 ml/min at week 6 postsham surgery. CONCLUSION: These results indicate that laser therapy does not induce angiogenesis and vascular remodeling in the ischemic hindlimb of a rabbit which exceeds that seen with a sham surgery.

Functional anatomy of the vagal innervation of the cervical trachea of the dog.

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.

Direct relaxant effects of intravenous anesthetics on airway smooth muscle.

Ketamine, at concentrations achieved with the usual clinical doses, has a direct relaxant effect on airway smooth muscle (ASM). This study investigates the dose-dependent direct relaxation effects of midazolam and propofol on both proximal and distal ASM compared with ketamine. The proximal and distal airways were dissected from eight mongrel dogs and cut into 2-mm rings. The rings were attached to pressure transducers and equilibrated in a Krebs-Ringer bicarbonate bath kept at 37 degrees C, pH 7.4, CO2 37 mm Hg, and PaO2 > 100 mm Hg. Optimal length was determined, a dose-response curve to acetylcholine was established, and the 50% effective dose (ED50) of acetylcholine was calculated. Ketamine, midazolam, or propofol were given in random order to each ring preconstricted with ED50 of acetylcholine in cumulative log incremental doses from 10(-6) to 10(-4) M. Relaxation response was the tension during anesthetic equilibrium, expressed as a percentage of the tension from ED50 of acetylcholine. The drug vehicles were tested for their effects on the ASM. No bronchorelaxation was seen with any of the intravenous anesthetics at 10(-6) M. Ketamine 10(-5) M produced at 17.9% +/- 2.1% relaxation in the distal ASM but had no effect on the proximal ASM. Neither propofol nor midazolam affected the ASM at 10(-5) M. The distal ASM was significantly (P < 0.005) more sensitive to 10(-4) M of all three drugs compared with the proximal ASM. In the proximal ASM, 10(-4) M of ketamine, midazolam and propofol reduced ASM tension by 14.9% +/- 4.4%, 19.0% +/-8.8%, and 14.7% +/- 5.5%, respectively, versus 36.4% +/- 3.2%, 58.6% +/- 6.1%, and 64.4% +/- 9.0% in the distal ASM. The drug vehicles had no effect on the ASM. We conclude that ketamine, midazolam, and propofol have direct relaxant effects on ASM. All three intravenous anesthetics have a greater direct relaxant effect on distal ASM than on proximal ASM. Only ketamine showed significant direct bronchorelaxing effects at concentrations that are likely to be achieved with the usual clinical dosing patterns.

Differential effects of desflurane and halothane on peripheral airway smooth muscle.

Volatile anaesthetics have been shown to have direct relaxant effects on airway smooth muscle. We have examined the effects of 0.9, 1.9, and 2.8 dog MAC of desflurane and halothane on isolated proximal and distal canine airways precontracted with acetylcholine. The proximal and distal airway smooth muscle relaxed with increasing concentration of each anaesthetic in a dose-related manner. Desflurane had a greater relaxant effect than halothane on the proximal airway only at 2.8 MAC. Desflurane relaxed the distal airway to a greater extent than halothane at 1.9 and 2.8 MAC. The distal airway smooth muscle was more sensitive to volatile anaesthetics than the proximal airway smooth muscle with either halothane or desflurane at all concentrations tested. This effect may be a result of differences in cartilage content, myosin content, epithelium-dependent effects, receptor density, myofilament sensitivity to Ca2+, sarcoplasmic reticulum Ca2+ control, or ionic fluxes in the proximal airway compared with the distal airway. The increased sensitivity of airway smooth muscle to desflurane compared with halothane is not known but may be related to possible differences in the effects of Ca2+ homeostasis.

Reflex effects of stimulation of sympathetic afferents on the triangularis sterni.

The purpose of this study was to determine whether contralateral inhibition of the triangularis sterni is produced by stimulation of intrathoracic sympathetic afferents. Dogs were anesthetized with sodium pentobarbital and placed on positive pressure ventilation. The chest was opened through a mid-sternal incision. Diaphragm and left and right triangularis sterni EMGs were recorded, post-vagotomy, before and during electrical stimulation of the left ventral ansa subclavia (VA), vagosympathetic trunk, ventrolateral and ventromedial cardiac nerves and, when present, the stellate cardiac nerve. Peak of the phasic diaphragm EMG and expiratory time were not significantly affected by stimulation of the VA. A significant decrease in inspiratory time was observed. Ipsilateral excitation and contralateral inhibition of the left and right triangularis sterni EMGs, respectively, were produced by stimulation of the VA. Stimulation of the other intrathoracic nerves produced a similar pattern of results. Conduction velocity determinations suggested that the afferents which produced the reflex responses are, at least in part, small A fibers.

Effects of halothane and isoflurane on antigen- and leukotriene-D4-induced constriction of guinea pig trachea.

We investigated the mechanism of the action of volatile anesthetics on the airway smooth muscle constricted by an antigen and leukotriene-D4 (LTD4). Excised tracheal rings from ovalbumin-sensitized guinea pigs were suspended in eight tissue baths. Halothane or isoflurane was aerated into four tissue baths, while the remaining four served as time controls. To assess the antispasmogenic activity of halothane and isoflurane, concentration-response curves for antigen and LTD, were constructed exposed to anesthetics and compared to controls. The spasmolytic activity of halothane and isoflurane was measured in the tracheal rings constricted by a single antigen challenge or by EC50 of LTD. Both halothane and isoflurane produced significant rightward shifts of ovalbumin and LTD, concentration-response curve with corresponding increases in the EC50 values. Halothane increased the EC50 value for LTD, from 5.38 +/- 0.43 x 10-9 M to 1.2 +/- 0.18 x 10-8 M, and for ovalbumin from 1.2 +/- 0.06 x 10-4 mg/ml to 3.03 +/- 0.28 x 10-4 mg/ml. Isoflurane increased the EC50 value for LTD, from 5.17 +/- 0.64 x 10-9 M to 8.98 +/- 1.01 x 10-9 M, and for ovalbumin from 1.21 +/- 0.09 x 10-4 mg/ml to 2.61 +/- 0.19 x 10-4 mg/ml. Furthermore, halothane and isoflurane significantly reduced the magnitude of the antigen-and LTD4-induced constriction. In 30 min intervals, 1% and 2% halothane reduced the magnitude of the ovalbumin-induced constriction by 32% and 50%, respectively, while isoflurane (2% and 4%) caused relaxation of 16% and 35%, respectively. The magnitude of LTD4-induced constriction was reduced by 17% and 24%, with 1% and 2% halothane, respectively. Isoflurane (2% and 4%) reduced this constriction by 25% and 25% respectively. In conclusion, halothane and isoflurane attenuate and prevent the constrictive response of airway smooth muscle to allergen and LTD. A direct, nonspecific dilating effect is suggested as the mechanism responsible for the observed effects.

Pigeon-serum-induced hypersensitivity pneumonitis in the dog.

Pigeon serum (PS) is one of the most common causes of hypersensitivity pneumonitis (HP). PS-induced HP was examined in a dog model. The dogs (n = 6) were immunized by i.m. injections of PS, followed by insufflation with aerosolized PS, while all control dogs (n = 3) received saline only. All animals insufflated with PS developed tachypnea 2-4 h after PS inhalation. After PS insufflation, a significant decrease in arterial oxygen tension (PaO2) was detected in sensitized dogs. No change in PaO2 was detected in sensitized dogs after saline or in the controls after PS insufflation. In intradermal skin tests with PS antigen, a positive skin reaction was found in 3/6 dogs in 30 min, and in 5/6 dogs in 6 and 48 h after the PS injections. Sensitized dogs showed a significant increase in PS-specific IgG in serum and lavage fluid (LF). In LF of sensitized dogs, an increase in the percentage of lymphocytes, eosinophils, and neutrophils was detected. Sensitized dogs developed chronic interstitial inflammation with lymphocytes, macrophages, plasma cells, and eosinophils in lungs. Granulomas with lymphocytes, histiocytes, and giant cells were detected in both the interstitium and the bronchiolar wall in the lungs of sensitized dogs. PaO2 was lowest in dogs showing the most severe interstitial inflammation in the lungs. The results indicate that dogs can be successfully used in immunologic and physiologic studies of PS-induced HP.

Inhibition of neutral endopeptidase potentiates compound 48/80-induced constriction of guinea-pig tracheal smooth muscle.

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic construction of guinea-pig tracheal smooth muscle. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on constriction induced by the non-immunological mast cell degranulator-compound 48/80. Phosphoramidon produced significant leftward shift of the compound 48/80 concentration-response curve with corresponding decrease in the EC50 value from 51 (28-80) micrograms/ml to 42 (20-72) micrograms/ml. When added during the compound 48/80-induced constriction, phosphoramidon significantly increased the magnitude of this constriction by 69.7% after 30 min, and 78.9% after 45 min. Phosphoramidon was ineffective in tracheal rings from tachykinin-depleted guinea pigs. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) and leukotriene receptor antagonist (ICI 198.615, 5 microM) significantly diminished the contractile response to compound 48/80 and prevented a phosphoramidon-dependent increase of this constriction. These results suggest that compound 48/80 induces the release of tachykinins by the stimulatory activity of histamine and leukotrienes. Anaphylactic release of tachykinins would therefore not depend directly on the antigen-antibody reaction.

Reflex effects of lung inflation on tracheomotor tone observed during apnea produced by the Hering-Breuer reflex.

Reflex effects of static pressure lung inflation (SLI) on tracheomotor tone (TT) were studied during apnea produced by the Hering-Breuer expiratory-facilitatory reflex. Anesthetized dogs were placed on cardiopulmonary bypass, and diaphragm electromyogram was used as an indicator of central nervous system inspiratory output. Tracheomotor tone (TT) was reflexly produced by chemoreceptor stimulation. The volume and frequency of the ventilator [phasic lung inflation (PLI)] were adjusted to produce nearly a maximum reflex decrease in TT. The increase in TT observed while PLI was withheld (0 mmHg tracheal pressure) for 1-2 min was used as the control response. SLIs were interspersed among sets of PLIs. Although SLI produced apnea, TT returned toward the control TT recorded during 0 mmHg tracheal pressure. TT observed during apnea was reflexly sensitive to further increases in SLI and to changes in chemoreceptor stimulation, which also affected the time course of the tracheomotor responses. These results suggest that the reflex decrease in TT produced by SLI and the Hering-Breuer expiratory-facilitatory reflex are mediated by different central mechanisms but may be from the same or different pulmonary receptors.

Topographical differences in the direct effects of isoflurane on airway smooth muscle.

Volatile anesthetics have a direct relaxant effect on airway smooth muscle, but it is not known whether this effect is similar throughout the bronchial tree. We studied the direct relaxation effect of isoflurane on isolated proximal (outer diameter [OD] 4-6 mm) and distal (OD 0.7-1.5 mm) canine airways precontracted with acetylcholine. Proximal and distal airway rings were suspended in tissue baths and stretched to their optimum length. A dose-response curve was obtained for each airway ring with log increments of acetylcholine. Maximum contraction was reached with 10(-2) mol/L of acetylcholine for the proximal airway smooth muscle (7.0 +/- 0.3 g of tension) and 10(-3) mol/L of acetylcholine for the distal airway smooth muscle (2.3 +/- 0.1 g of tension). Based on the dose-response curve, the ED50 of acetylcholine was calculated (1.26 +/- 0.37 x 10(-4) mol/L for proximal airway smooth muscle; 2.12 +/- 1.14 x 10(-5) mol/L for distal airway smooth muscle) and administered to each tissue bath, after which the stabilized response was recorded. A randomly selected dose of isoflurane (1, 2, or 2.6 dog minimum alveolar anesthetic concentration [MAC] was then administered to each bath and the relaxant responses were recorded. The proximal and distal airways relaxed with increased doses of isoflurane in a dose-related manner.

Phosphoramidon augments contraction of guinea pig tracheal smooth muscle induced by histamine and leukotriene-D4.

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. Anaphylactic release of tachykinin-like substances was indicated. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on contraction induced by mediators of anaphylaxis. Phosphoramidon significantly increased histamine- and leukotriene D4-induced contractions of tracheal rings from unsensitized animals (by 14 and 48%, respectively), but failed to alter the contractile responses to prostaglandins D2 and F2 alpha. In tracheal rings preincubated with tachykinin antagonist-[D-Pro4, D-Trp7,9]-substance P(4-11), or in capsaicin-desensitized tracheal rings, phosphoramidon did not change histamine- and leukotriene D4-induced contractions. In the second part of the study, performed on tracheal rings obtained from ovalbumin-sensitized guinea pigs, we examined the effects of phosphoramidon on contractile responses to histamine and leukotrienes which are released after antigen challenge. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl) or leukotriene receptor antagonist (ICI 198.615) prevented a phosphoramidon-dependent increase of antigen-induced contraction. These results indicate that histamine and leukotrienes may be involved in the anaphylactic release of tachykinin-like substances or other neutral endopeptidase substratum.

Phosphoramidon modulates effects of the 5-lipoxygenase inhibition on anaphylactic contraction of the guinea pig trachea.

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. It was suggested that anaphylactic release of tachykinin-like substances is likely to be responsible for the observed increases in tracheal contractions. To obtain additional information on the mechanisms responsible for anaphylactic release of tachykinins in guinea pig trachea, we examined the effects of phosphoramidon, an inhibitor of neutral endopeptidase, on contractile response to antigen after preincubation with the selective 5-lipoxygenase inhibitor AA-861. AA-861 (5 microM) significantly reduced ovalbumin-induced contraction, although the effect was not constant. A marked spontaneous increase in contraction was observed. Phosphoramidon (10 microM) produced significant increase of this contraction (27% after 30 min, and 33% after 45 min). The addition of H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) produced additional inhibition of the initial phase of antigen-induced contraction, while its later phase, apart from a spontaneous increment in magnitude, remained similar. Phosphoramidon (10 microM) increased the contraction by 26% after 30 min, and by 34% after 45 min. Since the effects of histamine and 5-lipoxygenase pathway products were prevented, we hypothesize that cyclooxygenase pathway products are responsible for the phosphoramidon-dependent increase in antigen-induced contraction. In accordance with previously reported ineffectiveness of contractile prostaglandins, we suggest that the relaxant prostaglandins are most important in mediating the release of tachykinins during the immediate hypersensitivity reaction in guinea pig trachea.

Reflex bronchodilation produced by phasic ventilation of the lungs.

The primary purpose of this work was to demonstrate whether oscillation of tracheal pressure in the range of normal breathing frequencies is more effective than static lung inflation in producing reflex bronchodilation. Secondarily, studies were conducted to determine a single factor that would integrate the reflex bronchodilator effects of frequency and tidal volume. Dogs were anesthetized and placed on cardiopulmonary bypass. After tracheal tone had been reflexly enhanced by chemoreceptor stimulation, oscillatory patterns of ventilation were produced around static pressure lung inflations of approximately 5.0 mmHg. The reflex bronchodilation produced by oscillation of lung volume was compared with that produced by static pressure lung inflation. Reflex bronchodilation produced by oscillation of lung volume was greater than that produced by static pressure inflation of the lungs and was strongly related to the maximum first time derivative of pressure (dP/dt, mmHg/s) observed, irrespective of whether the changes in the maximum dP/dt were produced by changes in the frequency or amplitude of the oscillations of tracheal pressure.

Inhibition of neutral endopeptidase augments anaphylactic constriction of guinea pig tracheal smooth muscle.

To determine whether tachykinins participate in antigen-induced constriction of tracheal smooth muscle, we examined the effects of a neutral endopeptidase inhibitor, phosphoramidon, the tachykinin antagonist (D-Pro4, D-Trp7,9,10)-substance P(4-11), and capsaicin-induced tachykinin depletion on the responses to antigen in tracheal rings from ovalbumin-sensitized guinea pigs. In these preparations, the antigen (ovalbumin, 0.1 microgram/ml) produced reproducible and durable constriction of tracheal smooth muscle. Incubation with phosphoramidon (10 min, 10 microM) prior to antigen challenge significantly augmented the magnitude of ovalbumin-induced constriction by 22% after 30 min and by 31% after 45 min. The addition of phosphoramidon at the plateau level of antigen-induced constriction produced a similar, significant increase in the magnitude of the constriction. Following incubation with tachykinin antagonist (D-Pro4,D-Trp7,9,10)-substance P(4-11) (5 microM), the contractile response of the tracheal rings to the antigen was not altered. Furthermore, the addition of phosphoramidon (10 microM) did not significantly affect this contraction. Similarly, neither tachykinin antagonist nor phosphoramidon altered the ovalbumin-induced constriction of the tracheal rings from capsaicin-treated guinea pigs. Based on these findings, we hypothesize that tachykinins or similar broncho-constricting neutral endopeptidase substrates were released from tachykinin-containing nerve endings during immediate hypersensitivity reaction in airways, manifesting a modest and delayed constrictive effect. Following alteration of endopeptidase activity, these substances could modulate the anaphylactic constriction of the airway smooth muscle.

The influence of isoflurane on the vascular reflex response to lung inflation in dogs.

Positive pressure ventilation can affect hemodynamic stability by neuroreflex-mediated activity. Inhalational anesthesia is known to attenuate the arterial baroreflex function; however, little information is known about the effect of volatile anesthetics on the lung inflation reflex. The influence of isoflurane on static lung inflation reflex-induced changes in venous capacitance and systemic resistance was investigated in dogs. After controlling carotid sinus pressure at 50 mmHg and initiating total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10 and 20 mmHg. The systemic vascular resistance index (SVRI) decreased by 0.04 +/- 0.03 and 0.13 +/- 0.03 mmHg.kg.min.ml-1 during tracheal inflation pressures of 10 and 20 mmHg, respectively. There as an accompanying change in systemic vascular capacitance index (SVCI) by 1.0 +/- 0.65 and 3.3 +/- 0.82 ml.kg-1 during tracheal inflation pressures of 10 and 20 mmHg. The addition of isoflurane decreased the reflex vascular response to lung inflation in a dose-dependent manner. A concentration of 1 MAC isoflurane administered via the cardiopulmonary bypass machine attenuated the change in SVRI to tracheal inflation pressures of 10 and 20 mmHg by 75% and 67%, respectively. Isoflurane at 1 MAC also reduced the reflex capacitance response to tracheal pressures of 10 and 20 mmHg by 36% each. Lung inflation-induced changes in SVRI and SVCI were abolished at isoflurane concentrations of 2 MAC. We conclude that under the conditions of this study, 1 MAC isoflurane was shown to attenuate lung reflex-induced changes in SVRI and SVCI and that at higher isoflurane concentrations (2 MAC) these reflex-induced changes were not seen.

Depression of baroreflex control of heart rate by halothane in growing piglets.

The purpose this study was to examine the effects of halothane on baroreflex control of heart rate in developing swine. Serial tests of baroreflex function were performed over the first 2 months of life in eight piglets in the conscious state and during anesthesia with 0.45, 0.9, and 1.35% halothane. Systemic blood pressure was increased with phenylephrine (pressor test) and decreased with nitroprusside (depressor test), and stimulus-response curves relating mean blood pressure to heart rate were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Halothane markedly depressed baroreflex sensitivity at all ages in a dose-dependent manner (conscious greater than 0.45% greater than 0.9%, 1.35%). Increasing age was accompanied by decreasing baroreflex sensitivity in both the conscious and the anesthetized states. The difference in baroreflex sensitivity between conscious and anesthetized states did not change with age for the depressor test (tachycardia response), but it did change with age for the pressor test (bradycardia response). For this test, conscious values converged toward anesthetized values at higher ages; therefore, there was relatively less depression by halothane at older ages. Halothane also decreased resting heart rate and decreased the limits and narrowed the range of the baroreflex heart rate response. Increasing age was accompanied by a decreasing resting heart rate and by decreasing limits and a narrowing range of the baroreflex response. The effect of halothane on heart rate variables was similar at all ages. Halothane decreased resting blood pressure and decreased the lower limit and widened the span of the baroreflex blood pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex ventilatory effects of KCl stimulation of lung receptors with sympathetic afferents.

The purpose of this study was to determine the reflex ventilatory effects produced by lung receptors with sympathetic afferent nerves. Seven dogs were anesthetized with sodium pentobarbital, placed on a ventilator, and vagotomized. The chest was opened through a mid-sternal incision. Diaphragm EMG (D-EMG), right and left triangularis sterni EMG (TS-EMG), systemic arterial blood pressure (BP), and tracheal pressure were recorded before and after the application of 2 M KCl to the right or left lung near the venous hilum. The reflex effects produced by KCl applied to the superior vena cava (SVC) and of mechanical distortion of the lungs were also studied. KCl applied to the right or left lung or right or left lung distortion produced significant increases in peak TS-EMG ipsilateral to the applied stimulus with no significant effects on the contralateral TS-EMG. BP, inspiratory time, expiratory time, or peak D-EMG were not significantly affected, except for a decrease in inspiratory time when KCl was applied to the left lung and a decrease in BP with distortion of the left lung. KCl applied to the SVC produced a significant reflex increase in the right TS-EMG. The primary reflex response to chemical stimulation of lung receptors with sympathetic afferents was an increase in expiratory muscle activity. Additionally, mechanical stimulation may also activate these receptors. Furthermore, receptors which produce similar reflex responses are located on the SVC. That the reflex responses produced by intrathoracic receptors with sympathetic afferents were unilateral suggests that spinal mechanisms are involved.

Development of baroreflex control of heart rate in swine.

The purpose of this study is to describe the developmental course of arterial baroreflex control of heart rate in swine. Tests of baroreflex function were performed with eight conscious piglets serially over their first 2 mo of life. Systemic blood pressure was raised with phenylephrine (pressor test) and lowered with nitroprusside (depressor test), and stimulus-response curves relating heart rate to mean blood pressure were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Baroreflex sensitivity decreased with increasing age. Baroreflex sensitivity was not different between pressor and depressor tests except when the piglets were greater than 52 d old and sensitivity was greater with the depressor test. The heart rates at threshold and saturation, and therefore the heart rate response range, shifted to lower heart rates with increasing age. This shift was more than can be accounted for by the simultaneously decreasing resting heart rate.

Chronic vascular catheters in growing piglets.

Chronic vascular catheterization of growing piglets is problematic because the animals grow rapidly and disrupt each others catheters when housed together. We successfully maintained chronic arterial and venous catheters in growing piglets for the first two months of life using the Vascular-Access-Port, a totally implantable catheter system. Two Vascular-Access-Ports (one venous and one arterial) were surgically placed in each of ten, 3-7 days-old piglets. Nine piglets survived the perioperative period, and for eight piglets the ports were successfully used for experimental purposes to infuse drugs, monitor arterial blood pressure and obtain blood samples for approximately two months. During this period the piglets averaged an eight-fold increase in body weight. This technique of chronic vascular catheterization is useful for experiments employing conscious, growing animals.

Influence of lung inflation reflex on vascular capacitance in the systemic circulation.

The effects of sustained lung inflation on systemic vascular capacitance (SVC), systemic vascular resistance (SVR), and cardiac sympathetic efferent nerve activity (SENA) were investigated in anesthetized dogs. By use of a total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10, 15, and 20 mmHg. Tracheal pressures of 10, 15, and 20 mmHg increased system vascular capacitance by 1.4, 3.1, and 4.3 ml/kg and decreased systemic vascular resistance by 0.11, 0.15, and 0.16 mmHg.kg.min-ml-1, respectively, at low carotid sinus pressure (CSP) of 41 mmHg. SENA showed a concomitant decrease. Bilateral vagotomy attenuated the change in SVR by 69%, SVC by 62%, and SENA by 97% when lungs were inflated to a tracheal pressure of 20 mmHg at a low CSP. These results indicate that lung inflation causes a reflex induced increase in SVC as well as a decrease in both SVR and SENA. The lung inflation reflex is mediated primarily through vagal afferent nerve fibers with a small contribution from other afferent nerve pathways.