Heart-lung interactions: the sigh and autonomic control in the bronchial and coronary circulations.

1. The Darwin hypothesis that human and animal expressions of emotion are the product of evolution and are tied to patterns of autonomic activity specified to progress the emotion remains under challenge. 2. The sigh is a respiratory behaviour linked with emotional expression in animals and humans from birth to death. The aim of the present study was to explore Darwin's hypothesis with respect to tied autonomic activity underlying sigh-induced changes in the bronchial and coronary circulations. 3. Awake dogs were prepared using pulsed ultrasonic flow probes on the right bronchial artery, parent intercostal artery and brachial artery, or on the right, circumflex and anterior descending coronary arteries. Central venous (CVP) and arterial pressures (AP) were measured; heart rate and flow conductances were derived. Three spontaneous sighs were monitored before and during random blockade of individual and combinations of cholinoceptors, alpha-adrenoceptors and beta-adrenoceptors using methscopolamine, phentolamine and propranolol infusions. The data were subject to a 2(3) factorial analysis. 4. A spontaneous sigh is marked by a transient fall and return (< 3 s) in CVP of 18 mmHg (from 4 +/- 1 to -14 +/- 2 mmHg), usually followed by apnoea lasting 23 +/- 2 s. There is an immediate tachycardia and small rise in AP (phase 1) then, during apnoea, bradycardia and a fall in AP (phase 2). During phase 2, bronchial and coronary blood flow and conductance rise two- to three-fold over 30s (peak at 8s). The vascular changes are absent in parent intercostal and brachial beds.

Effect of fentanyl on baroreflex control of circumflex coronary conductance.

1. Fentanyl, a synthetic mciro-opioid receptor agonist, is the preferred induction and maintenance anaesthetic agent in cardiac surgery. 2. Its actions on myocardial blood flow are poorly understood. There are reports of intra-operative myocardial ischaemia. Its reported actions on cardiorespiratory control vary widely, but do involve hypertension, bradycardia and peripheral vasoconstriction. 3. Accordingly, the postulate that fentanyl would cause coronary vasoconstriction and myocardial disadvantage was examined in awake dogs with a continuous wave Doppler flow probe mounted on the circumflex coronary artery. 4. Continuous intravenous infusion of fentanyl citrate (550 ng/kg per min) raised plasma concentrations of fentanyl to 3.37 ng/mL in a linear fashion at 20 min. There was a fall in core temperature of 0.7 degrees C and, although no apparent depression of ventilation or fall in arterial or coronary sinus PO2, there was a rise in PCO2 and H+ concentration. Some dogs salivated and panted transiently. Thus, fentanyl may reset temperature regulation in low doses but, at higher doses, is associated with metabolic acidosis. 5. In sinus rhythm, the arterial pressure of the dogs fell slightly, then rose to 115% of resting control. Circumflex flow and conductance rose early, then conductance steadily declined to 83%. Heart rate fell, then rose before returning to pre-infusion levels. The early circumflex coronary vasodilator effects, but not the later vasoconstrictor effects, were reduced in dogs with paced hearts. 6. In dogs with paced hearts, a dose-effect study using 138, 275, 550 and 1100 ng/kg per min fentanyl suggested that, at low plasma concentrations of 1-2 ng/mL, vasodilatation does occur in both coronary and systemic circulations; however, at higher doses, intense coronary and systemic vasoconstriction supervenes. 7. The dose-response effect of fentanyl on arterial baroreflex control of circumflex conductance was examined during the immediate 8 s circumflex vasodilator response to a step rise in aortic pressure caused by inflation of an intra-aortic balloon. At low plasma concentrations of fentanyl, baroreflex control of circumflex conductance appears to be enhanced but, with increasing plasma concentrations of fentanyl, appears to be depressed. 8. Therefore, the effects of fentanyl are dose dependent. At low plasma concentrations, left ventricular blood flow and its baroreflex control is enhanced but, at higher concentrations, it is depressed.

Effects of anaesthesia on regional coronary control mechanisms.

1. The regional coronary circulation is under the control of local metabolic and myogenic factors, but is also influenced by autonomic systems, including sympathetic and parasympathetic nerves. 2. General anaesthetic agents influence not only local control through changes in metabolic demand, but also neural control through suppression of autonomic influence. 3. Anaesthetic agents have differing effects on reflex control systems, which are dependent on coronary territory and ventricular rate. 4. Effects of anaesthesia should be taken into account when interpreting results in anaesthetized models of coronary control.

Recent views on integrated coronary control: significance of non-uniform regional control of coronary flow conductance.

1. Previous work from this laboratory and others has shown that powerful autonomic influences modulate coronary flow. In particular, the parasympathetic nervous system produces vasodilatation when activated by baroreceptors via the vagus nerve. 2. Differences exist in baroreflex coronary vasodilator mechanisms among the right, circumflex and anterior descending coronary vascular beds in the awake chronically instrumented dog. 3. Our hypothesis is that neurogenic acetylcholine acting from the adventitial side and endothelial nitric oxide from the luminal aspect of coronary smooth muscle compete with powerful intrinsic myogenic constrictor mechanisms to regulate regional flow conductance. 4. There is also increasing evidence that heterogeneity of control systems exists in different-sized coronary vessels within an individual coronary vascular bed. 5. It is concluded that coronary vessels in vascular beds can no longer be assumed to respond in a uniform manner to neural, myogenic, metabolic or humoral factors. 6. These new perspectives of regional control mechanisms have important implications for understanding pathophysiological mechanisms inducing and sustaining tachyarrhythmias involved in ischaemic heart disease.

Halothane attenuates myogenicity in the rabbit ear artery.

UNLABELLED: The aim of this study was to test the hypothesis that halothane interferes with the myogenic response to an increase in intraluminal pressure. Myogenic responsiveness refers to the intrinsic property of vascular smooth muscle to dilate and then constrict in response to an increase in intraluminal pressure, in an attempt to maintain vessel diameter. Vessel segments taken from the rabbit central ear artery were cannulated, pressurized to 60 mm Hg, and perfused with and suspended in Krebs solution. After exposure to extraluminal l-norepinephrine, vessels contracted to an initial diameter (Di) and were subjected to intraluminal pressure increases to 100 mm Hg. Myogenic reactivity was assessed by measurement of the extent of dilatation after the pressure increase from Di to a maximal diameter (Dm) and then the constriction and recovery (against the pressure increase) to a final (Df) diameter. Myogenicity was further assessed by determining the rate of return of the vessel diameter (angle of recovery) and vessel recovery (defined as Dm - Df/Dm - Di) and expressed as a percentage. Myogenicity was determined before and after exposure to halothane in concentrations of between 1-5%. Halothane significantly attenuated the myogenic response at all concentrations studied. The effect of halothane was maximal at a concentration of 5% where there was virtual abolition of the myogenic response with recovery assessed at 6+/-2.7% (SEM), compared with control (98+/-2.5%, P < 0.05). The angle of recovery was likewise attenuated. These data suggest that halothane, in a dose-dependent manner, attenuates myogenicity in the isolated rabbit ear artery preparation. IMPLICATIONS: Blood pressure is controlled partially by the myogenic response. This refers to the capacity of arteries to dilate and then constrict in response to pressure increase. Using arteries from rabbits, we have shown that administration of halothane reduces or abolishes this response. This observation may be a contributing factor to hypotension caused by halothane.

Venous hydrostatic indifference point as a marker of postnatal adaptation to orthostasis in swine.

The postulate that venous adaptation assists postural baroreflex regulation by shifting the hydrostatic indifference point (HIP) toward the heart was investigated in eight midazolam-sedated newborn piglets. Whole body head-up (+15, +30, and +45 degrees ) and head-down (-15 and -30 degrees ) tilt provided a physiological range of orthostatic strain. HIP for all positive tilts shifted toward the heart (P < 0.05), +45 degrees HIP shifted most [6.7 +/- 0.3, 5.9 +/- 0.5, and 3.6 +/- 0.3 (SE) cm caudal to right atrium on days 1, 3, and 6, respectively]. HIP for negative tilts (3.0 +/- 0.2 cm caudal to right atrium) did not shift with postnatal age. Euthanasia on day 6 caused 2.1 +/- 0.3-cm caudal displacement of HIP for positive and negative tilts (P < 0.05). HIP proximity to right atrium was not altered by alpha-, beta-adrenoceptor and cholinoceptor blockade on day 5. It is concluded that early HIP migration reflects enhancement of venous pressure control to head-up orthostatic strain. The effect is independent of baroreflex-mediated adrenoceptor and cholinoceptor mechanisms.

Baroreflex control of coronary blood flow varies regionally in awake dogs.

1. Baroreflex responses to changes in aortic pressure were measured simultaneously in three main coronary regions of awake dogs. 2. Pulsed Doppler flow probes were mounted at prior surgery on the right, circumflex and anterior descending coronary arteries; the animals were placed in complete heart block and the left ventricle was paced. After 2-4 weeks recovery, baroreflexes were evoked by inflating a balloon catheter placed in the mid-thoracic aorta via the femoral arteriotomy. Flow and pressure data were collected at rest, and during acute (8s) and steady-state (25s) baroreflex challenge. 3. Changing ventricular rate alone caused a fall in aortic pressure at low rates; however, over the range 60 to 180 b.p.m., circumflex and anterior descending coronary flow and conductance changed directly with ventricular rate, but right coronary flow and conductance remained unchanged. 4. Acute aortic pressure elevation increased flow at 8s in all beds at all rates. Conductance effects at 60 b.p.m. were negligible in all three beds, but rose at 100 and 180 b.p.m. in the right and circumflex beds. 5. Sustained aortic pressure elevation (25s) caused flow to return towards control in all beds ventricular rates, but in the right coronary at 60 b.p.m. flow fell below control. Conductance at this time was unchanged at all rates in the anterior descending bed, fell modestly in the circumflex, and decreased to below resting in the right coronary bed. 6. Baroreflex control of coronary flow and conductance thus varies between territories, and within territories, depending on ventricular rate. The right coronary bed appears to be regulated by a bidirectional, baroreflex-linked mechanism, which is functionally opposite in action to that found in most vascular beds.

Limitations of a pulsed Doppler velocimeter for blood flow measurement in small vessels.

The performance of a new and simplified flow probe construction and the Iowa 545C-4 pulsed Doppler velocimeter was evaluated for measurement of blood flow over several months in small arteries of awake animals. Calibrations were performed over a wide range of intraluminal pressures and physiological flow velocities. Pressure-dependent differences in slope of the Doppler shift-volume flow relationship were detected in some probes. Signal strength was maintained at hematocrits > 10%. Distortion of pulsed Doppler signal peaks occurred in the conscious rabbit at peak aortic velocities, at which Reynold's number for turbulence was exceeded and the Doppler shift surpassed the Nyquist limit of 31.25 kHz for the velocimeter. Although the Doppler shift-volume flow relationship is linear at < 5 kHz, in some cases at higher Doppler shifts and blood flow velocities the relationship may become nonlinear, thus causing the volume flow rate to be underestimated by up to 38%. The cause of this phenomenon may be "aliasing" and/or the consequence of the range control capability of the velocimeter selectively sampling changing velocity profiles and flow disturbances in the central stream at higher velocities.

Impedance cardiography for cardiac output measurement: an evaluation of accuracy and limitations.

The Kubicek thoracic cylinder model of impedance cardiography (IC) for measuring beat-by-beat stroke volume (SV) was evaluated in controlled studies using the electromagnetic flowmeter (FM) as the reference technique. Assuming the validity of the Kubicek equation for stroke volume calculation, IC stroke volume was found to be a linear function of EM values at any one haematocrit over a wide range of SV, but the slope of the relationship fell as haematocrit fell. Experiments using the same equation in dogs, in which blood resistivity in vivo (rho tau) was made the dependent variable, and the EM-derived value was used for stroke volume, showed that rho tau was almost constant over a wide range of haematocrits. These findings were supported by studies in man and rabbit where Fick and thermodilution-derived values were used for stroke volume. When these data were applied to normotensive and hypertensive human subjects with normal hearts and lungs in controlled studies at rest, during tilting, with drug therapy and on exercise, IC measured stroke volume and cardiac output with a variability at least as good as the 9-11% acceptable for clinical use. This conclusion applied to thoracic configurations of different sizes and shapes from adult man to the neonate. In chronic disease states, while assessments of relative changes are valuable, absolute data are questionable. Further research is required under these conditions, as it is also for other models of IC, which are based on different assumptions.

Modern inhalational anaesthetic agents. A review of halothane, isoflurane and enflurane.

The intelligent use of modern inhalational anaesthetic agents requires a detailed knowledge of their pharmacology. Currently, the volatile agents in most-common use in Australia are halothane, isoflurane and enflurane. This brief review analyses the similarities and differences in the pharmacological properties of these three drugs in order to provide practitioners with the necessary background knowledge to assist in the selection of an appropriate anaesthetic agent for a given clinical problem.

Lesions of A1 noradrenergic cells affect AVP release and heart rate during hemorrhage.

The role of A1 noradrenergic cells of the ventrolateral medulla in the changes in mean arterial pressure (MAP), heart rate (HR), and plasma arginine vasopressin (AVP) after slow continuous hemorrhage (2% blood vol/min up to 35%) was examined by comparing responses in conscious rabbits before and 3 wk after a sham operation or A1 lesions. In the control experiments, MAP fell minimally up to the withdrawal of 20% of blood volume after which it fell abruptly to 20-30 mmHg below control by the 35% level. Plasma AVP increased nonlinearly during progressive hemorrhage with significant increases occurring only after 25% of blood volume was removed. In contrast, HR increased linearly after the onset of bleeding. After A1 lesions, which destroyed 84% (range 80-94%) of the noradrenergic cells, the amount of AVP released and the tachycardia during hemorrhage were reduced by 83 and 61%, respectively (P less than 0.005), but the fall in MAP was minimally affected. Basal values of MAP, HR, or plasma AVP were not affected by the lesions. These results suggest that during hemorrhage in conscious rabbits A1 noradrenergic neurons are important for the secretion of AVP and the reflex tachycardia but play little role in the maintenance of blood pressure.

Cardiac and arterial baroreceptor influences in release of vasopressin and renin during hemorrhage.

We studied the role of arterial and cardiac baroreceptors on mean arterial pressure (MAP) and release of arginine vasopressin (AVP) and plasma renin activity (PRA) during hemorrhage in conscious rabbits. Each rabbit was bled at 2% of its blood volume (BV) per minute until 35% had been removed, after which the blood was reinfused. Each rabbit was studied on three occasions, 7 days apart, and in each experiment, BV-MAP and BV-hormone response curves were constructed. The response to hemorrhage was examined when the input from arterial and cardiac baroreceptors were both intact; arterial baroreceptors only were intact (cardiac receptors were blocked with intrapericardial procaine); cardiac receptors only were intact (after sinoaortic denervation); neither receptor was intact. Resting AVP and PRA levels were unaffected by the various deafferentation procedures. AVP steeply increased only after more than 25% BV had been removed; this response was entirely mediated by cardiac baroreceptors. Increases in PRA occurred at BV loss greater than 15% and were largely independent of baroreceptor input. Maintenance of MAP during hemorrhage was mostly due to drive from the arterial baroreceptors. Thus AVP secretion during hemorrhage contributes little to the maintenance of MAP, and the hypovolemic stimulus to AVP release comes entirely from the cardiac baroreceptors.

Selective manipulation of neurohumoral control of the cardiac pacemaker by drugs given intrapericardially.

A technique of intrapericardial administration of beta-adrenoceptor and muscarinic cholinergic receptor antagonist drugs has been tested in conscious rabbits. Intrapericardial propranolol or atenolol (50 micrograms/kg) had the same effect on isoprenaline heart rate dose-response curves and on the sympathetic component of the arterial baroreceptor-heart rate reflex as did conventional, 5-fold greater, intravenous doses of the drugs. The action of intrapericardial propranolol was attributable to its (-)isomer. Intrapericardial propranolol (50 micrograms/kg) had little effect on ventricular contractility. Plasma levels of propranolol and atenolol after intrapericardial administration were, respectively, 7- and 40-fold less than after the usual intravenous doses. Intrapericardial hyoscine methyl bromide (10 micrograms/kg) abolished baroreflex vagal effects on heart rate as effectively as did the conventional, 5-fold greater, intravenous dose. The duration of receptor blockade by both classes of drugs when given intrapericardially was at least 2 hr. We conclude that the rapid diffusion of beta-adrenoceptor and muscarinic cholinergic receptor blocking drugs from the pericardial sac to receptors on the sinoatrial cardiac pacemaker, and their prolonged actions, provides a useful technique for preventing the actions of the sympathetic and vagus nerves, and of circulating catecholamines, on the chronotropic functions of the heart.

Central nervous system 5-hydroxytryptamine and noradrenaline specificity of ear vascular and ventilation reflexes in thermoregulating rabbits.

Contrasting hypotheses of mammalian thermoregulation were tested in unanesthetized rabbits in relation to the role of the central nervous (CNS) monoamines 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in regulating lung function and ear skin blood flow (Doppler flowmeter). Normal rabbits and rabbits with CNS depletion of 5-HT and NA (caused by the neurotoxins 5,7-dihydroxytryptamine and 6-hydroxydopamine) were studied in an airconditioned chamber at ambient temperatures of 12 degrees, 22 degrees and 35 degrees C. The results suggest that CNS 5-HT plays an excitatory role in the heat conservation mechanism of cold-induced ear skin vasoconstriction, and that this effect is inhibited by CNS NA to cause heat dissipation during heat stress. Both CNS 5-HT and NA appear to exert a mild inhibitory restraint on ventilation even during heat stress. The data support the theory that CNS 5-HT is concerned with heat conservation and CNS NA with heat loss mechanisms in the cutaneous circulation, and that both monoamines moderate heat loss through panting. CNS monoamine-dependent thermoregulation in the rabbit thus resembles the model postulated for the cat, dog and monkey rather than, as previously proposed, for the sheep and goat.

Role of central nervous system monoamines in cardiopulmonary effects of Althesin in rabbit and man.

The steroid induction agent, Althesin, infused intravenously in light anesthetic doses in otherwise unsedated man (84 micrograms kg-1 min-1) and rabbit (140 micrograms kg-1 min-1) causes similar autonomic and somatic effects. In the rabbit, the rise in heart rate (mainly due to central vagal blockade) and the selective depressant effects on respiratory rate are independent of CNS 5-hydroxytryptamine and noradrenaline. The rise in arterial pressure and the fall in hindlimb conductance is dependent on CNS 5-hydroxytryptamine and noradrenaline synthesizing neurons, which are probably arranged in series. These findings provide a working hypothesis for the mechanisms of action of Althesin on central cardiopulmonary controls in man.

Suprabulbar and bulbar integration of ventilation and ear vascular control during thermoregulation in the rabbit.

Suprabulbar and bulbospinal integration of cardiorespiratory responses to cold and heat stress was studied in groups of normal, thalamic and pontine rabbits. The animals sat in an airconditioned environmental chamber in which ambient temperature (TA) was maintained sequentially at 22 degrees C, 12 degrees C, 22 degrees C and 35 degrees C, with an accuracy of +/- 1 degree C. Neither thalamic nor pontine rabbits could maintain core temperature in cold or heat. At TA 35 degrees C, thalamic and pontine animals did not pant, indicating that telencephalic responses were necessary for the integration of mechanisms promoting respiratory heat loss. Thalamic animals, however, could inhibit ear vascular sympathetic tone in the heat, but the response was absent in pontine animals, suggesting diencephalic responses were essential for the integration of mechanisms promoting ear skin heat loss. Thus, the neural adjustments to thermal stress depend on mechanisms of integration distributed longitudinally throughout the central nervous system, and different components of the reflex cardiorespiratory response depend on different sites in the central nervous system for their full expression.

Effects of changing haematocrit, ventricular rate and myocardial inotropy on the accuracy of impedance cardiography.

1. The accuracy and limitations of the non-invasive impedance cardiograph technique were examined in dogs with electromagnetic flow-transducers mounted on the aortic root over a wide range of physiological conditions of anaemia, heart rate, stroke volume and myocardial inotropy. 2. The in vivo blood resistivity (rho-haematocrit relationship is linear and slightly inverse, and is thus opposite to the curvilinear, direct relationship of the bench-derived rho-haematocrit relationship. At haematocrit 41%, in vivo rho is 135 ohm.cm (s.e.m. = 1.0, n = 134) and rises only to 143 ohm.cm (s.e.m. = 1.6, n = 134) as haematocrit falls to 26%. 3. When in vivo rho is used in the Kubicek formula for stroke volume (SV) calculation, the instrument is linear and accurate for heart rates over 38-156 min-1. Thus 82% of all points fall within +/- 20% of the line of equal value over stroke volumes ranging from 8-46 ml (N = 3, n = 105). The standard error of the estimate for pooled data is +/- 2% of the mean impedance stroke volume value of 22.2 ml. The instrument tends to overread at heart rates lower than 60 min-1.

Thoracic resistivity for stroke volume calculation in impedance cardiography.

Blood resistivity (rho) values used in the Kubicek formula for stroke volume (SV) calculation by impedance cardiography are bench derived and do not take into account complex blood velocity movements and dynamic hematocrit changes in systole. In this study, the relevance of rho has been questioned. Thoracic resistivity (rho tau) has been calculated in dogs from the rearranged Kubicek formula: rho tau = (SV . ZO2)/(L2 dZ/dtmax.T), where SV was measured by the electromagnetic flowmeter (EM). Hematocrit (Hct) in the dog was varied by hemorrhage and infusion. In contrast to the direct and exponential bench rho-Hct relationship, rho tau varies inversely with Hct, but by no more than +6.3 omega . cm (at Hct 26%) and -11.8 omega . cm (at Hct 66%) about a mean rho tau of 135 +/- 1.0 omega . cm (at Hct 40%). Impedance SV calculated using rho tau over a wide range of SV bears a linear relationship to EM values with a 95% prediction limit for a single SV estimate of +/- 0.84 about a mean value of 26.9 ml. The findings suggest that rho tau is virtually constant during a variety of physiological disturbances.