Effect of ventilation and perfusion imbalance on inert gas rebreathing variables

The effects of ventilation-to-perfusion (VA/Qc) maldistribution within the lungs on measured multiple gas rebreathing variables were studied in 14 dogs. The rebreathing method (using He, C18O, and C2H2) allows for measurements of pulmonary capillary blood flow (Qc), diffusing capacity (DLco), lung gas volume, and the combined pulmonary tissue and capillary blood volume (VTPC). VA/Qc imbalance was created by reversibly occluding the right main pulmonary artery or by reversibly obstructing the left main bronchus in eight dogs. Six additional dogs were ventilated with 10 cmH2O positive end-expiratory pressure (PEEP) to create a bimodal distribution of VA/Qc within the lungs. No significant alterations in computed rebreathing variables, except for a small (14%) decrease in DLco, occurred during right main pulmonary artery occlusion, whereas obstruction of the left main bronchus caused parallel decreases (mean of 46%) in all rebreathing variables. Ventilation with 10 cmH2O PEEP for 3 h caused no alterations in VTPC when compared with postmortem determinations of total lung water. Thus marked alterations in distribution of Qc or creation of VA/Qc maldistributions with PEEP caused no significant changes in rebreathing parameters, whereas obstruction of the left main bronchus resulted in decreases in all rebreathing values consistent with the presumed size of the ventilation defect. Thus it appears that rebreathing estimates of VTPC and other rebreathing parameters are accurate in states of moderate VA/Qc maldistribution within the lung.     

Role of the rise of pressure in the pulmonary artery in the distribution of perfusion and gas exchange in bronchial obstruction

The experiments on the dogs revealed that the damage of lobar bronchus conduction resulted in the decrease of O2 tension in pulmonary venous blood of this lobe. The decrease in the ventilation and blood flow was found in the zone of obstruction by using tracers 133Xe and 99mTc. The pressure rise in the pulmonary artery caused by the spread of bronchial obstruction is one of the factors promoting the redistribution of perfusion into the reserve zones of lungs. The decrease of pressure by the ganglio-blocking preparation results in the increase of arterial hypoxemia.     

Acute increases in anastomotic bronchial systemic to pulmonary blood flow due to generalized lung injury

Since pulmonary blood flow to regions involved in adult respiratory disease syndrome (ARDS) is reduced by hypoxic vasoconstriction, compression by cuffs of edema, and local thromboses, we postulated that the bronchial circulation must enlarge to provide for the inflammatory response. We measured anastomotic bronchial systemic to pulmonary blood flow [QBr(s-p)] serially in a lung lobe in 31 open-chest dogs following a generalized lobar injury simulating ARDS. The pulmonary circulation of the weighed left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in anesthetized dogs. QBr(s-p) was measured from the amount of blood which overflowed from this closed vascular circuit corrected by any changes in the lobe weight. The LLL was ventilated with 5% CO2 in air. The systemic blood pressure (volume infusion), gases, and acid-base status (right lung ventilation) were kept constant. We injured the LLL via the airway by instilling either 0.1 N HCl or a mixture of glucose and glucose oxidase or via the pulmonary vessels by injecting either alpha-naphthylthiourea or oleic acid into the LLL pulmonary artery. In both types of injury, there was a prompt rise in QBr(s-p) (mean rise = 247% compared with control), which was sustained for the 2 h of observation. The cause of this increase in flow was studied. Control instillation of normal saline into the airways or into the pulmonary vessels did not change QBr(s-p) nor did a similar increase in lobar fluid (weight) due to hydrostatic edema. Neither cardiac output nor systemic blood pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship

The present study is an investigation of the effect of beta-adrenergic receptor stimulation by isoproterenol on pulmonary vascular capacitance. The experiments were done in six intact-chest, anaesthetized dogs in which pulmonary and cardiac blood volumes were assessed by blood pool scintigraphy. Isoproterenol (0.150 microgram.kg-1.min-1) significantly (p less than 0.005) lowered pulmonary capillary wedge pressure (PPCW) and pulmonary artery pressure (PPA) but did not significantly change pulmonary blood volume (PBV). Left ventricular end-diastolic pressure and total cardiac volume both significantly (p less than 0.005) decreased. Pulmonary vascular volume-pressure (V-P) relationships before and during isoproterenol were described by means of blood transfusions and hemorrhage. In individual dogs the PBV-PPCW and the PBV-(PPCW + PPA)/2 relationships were significantly shifted upward by isoproterenol (p less than 0.05 or less); slope changes were variable. Pooled data from all dogs also showed a significant (p less than 0.001) upward shift in the pulmonary vascular V-P relationship regardless of which measure of distending pressure was used. These results suggest that beta-receptor stimulation by isoproterenol increases pulmonary vascular capacitance by increasing the unstressed volume.     

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.     

Pulmonary hypertension induced with an intra-arterial balloon: an alternate mechanism

The Laks catheter is a triple-lumen balloon catheter used to distend the canine main pulmonary artery while recording right ventricular pressure and the arterial pressure distal to the balloon. A rise in arterial pressure reported to occur during distension has been attributed to vasoconstriction rather than passive obstruction by the balloon. We tested this in six anesthetized dogs by inflating the Laks catheter-balloon while recording pressure distal to the balloon from the Laks catheter as well as from additional catheters in right and left pulmonary arteries placed retrogradely through lobar branches following thoracotomy. We found that balloon inflation increased pressures in the arterial port of the Laks catheter and in the left pulmonary artery catheter but reduced it in the right pulmonary artery. Tightening a snare around the right pulmonary artery had the same effects on pressures. Similar results were obtained while cardiac output was controlled by left ventricular bypass perfusion in four dogs. We conclude that the Laks catheter-balloon obstructs flow to the right lung and that the arterial pressure rise recorded in it during balloon inflation cannot be distinguished from that caused by occlusion of the right pulmonary artery.     

Early radiation response of the canine heart and lung

In this study three groups of four adult beagle dogs were irradiated with a 12-Gy single dose to the thorax. The fields used were the entire thorax, the entire thorax with a heart block in place, and the heart with one-third of the lung volume. The response of the lung was evaluated by cellular and biochemical analysis of sequential bronchoalveolar lavage fluids, blood gas analysis, physical examination, and histopathology. Sparing a small volume of lung improved survival. Cardiac function was evaluated by right heart catheterization, echocardiography, physical exam, and histopathology. Pulmonary artery pressure was increased in all dogs, mean systemic artery pressure was decreased in all dogs, and no difference could be shown among the groups. These effects are likely secondary to a reduced pulmonary capillary volume. Stroke volume was significantly deceased in dogs that had their hearts included in the field but not in dogs with their hearts shielded. This effect was not thought to be secondary to lung injury. The influence of lung irradiation on cardiac function was limited to pulmonary hypertension. Pulmonary hypertension may be enhanced by the release of vasoactive compounds. Pulmonary hypertension may contribute to radiation-induced heart failure.     

Causes of experimental pulmonary hypertension in rats.

Experimental pulmonary hypertension was induced in young male rats by means of tracheoconstriction and repeated injections of aqueous bean (Phaseolus vulg.) extract into the trachea. After 120 days, the blood pressure of the experimental and control animals was measured in the pulmonary artery with a shaped polyethylene catheter, without opening the chest. In all the experimental animals the blood pressure in the pulmonary artery was higher than in the controls. The mean pressure in the pulmonary artery of the experimental rats was 25 +/- 1 torr and in the controls 16 +/- 0.4 torr. The right ventricle of the experimental animals was larger than in the controls. No difference was found between the systemic blood pressure values, measured in the femoral artery, in the experimental animals and the controls. The experimental animals had a faster heart rate. Cardiac output, measured by the dye dilution method, was the same in the control and experimental animals and there was likewise no difference in the PO2 PCO2 and pH values in the arterial blood. The inhalation of oxygen instead of air did not affect the blood pressure in the pulmonary artery. The pulmonary blood vessels were evaluated quantitatively in histological sections of the experimental and control animal's lungs. There was no different between the thickness of the media of the distal pulmonary vessels, expressed as a percentage of the outer diameter of the vessel, in the experimental animals and the controls. A media thicker than 7% was found in 15% of the evaluated vessels from experimental animals and in 8% of those from the controls. No correlation between the mean thickness of the media and the mean blood pressure in the pulmonary artery was found in any of the animals.     

Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive depressor drugs injection

The character and values of changes of the pulmonary hemodynamics and venous return following acetylcholine, histamine and isoproterenol intravenous injection were studied in acute experiments on the anesthetized cats. After depressor drugs injection the character and values of changes of pulmonary artery pressure and flow were different. In 67% cases the pulmonary artery pressure was decreased, and in 33%--it was elevated, meanwhile the pulmonary artery flow was decreased in 48% cases and it was increased in 52%, i.e., in the equal number of observations. Thus, following depressor drugs intravenous injection, hemodynamic mechanisms of the changes of pulmonary artery pressure and flow are different. The character and values of changes of the pulmonary artery pressure are correlated with the changes of pulmonary vascular resistance and are not dependent with the left atrial pressure shifts. The changes of the pulmonary artery blood flow are caused by the changes of the venous return and are not correlated with the changes of the right and left atrial pressure.     

Alveolar pressure in fluid-filled occluded lung segments during permeability edema

In a model of increased hydrostatic pressure pulmonary edema Parker et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 267-276, 1978) demonstrated that alveolar pressure in occluded fluid-filled lung segments was determined primarily by interstitial fluid pressure. Alveolar pressure was subatmospheric at base line and rose with time as hydrostatic pressure was increased and pulmonary edema developed. To further test the hypothesis that fluid-filled alveolar pressure is determined by interstitial pressure we produced permeability pulmonary edema-constant hydrostatic pressure. After intravenous injection of oleic acid in dogs (0.01 mg/kg) the alveolar pressure rose from -6.85 +/- 0.8 to +4.60 +/- 2.28 Torr (P less than 0.001) after 1 h and +6.68 +/- 2.67 Torr (P less than 0.01) after 3 h. This rise in alveolar fluid pressure coincided with the onset of pulmonary edema. Our experiments demonstrate that during permeability pulmonary edema with constant capillary hydrostatic pressures, as with hemodynamic edema, alveolar pressure of fluid-filled segments seems to be determined by interstitial pressures.     

Distribution of pulmonary vascular resistance during lactic acid infusion in dogs

We sought to determine the longitudinal distribution of pulmonary vascular resistance (PVR) in acute lactic acidosis utilizing pulmonary artery and vein balloon occlusion techniques (Holloway et al. J. Appl. Physiol. 54: 840-851, 1983). In anesthetized dogs, both a systemic vein (I-V) infusion and systemic artery (I-A) infusion of L-lactic acid were studied to control for potential effects of factors other than pH on PVR. During progressive I-A infusion (n = 9) to a pH of 6.94 +/- 0.06 there was no significant change in PVR or its distribution. In contrast, I-V infusion (n = 9) to a pH of 7.08 +/- 0.09 increased median PVR from 3.6 to 21.7 mmHg.1(-1).min (P less than 0.001), due to an increase in middle segment resistance (0.0-15.4 mmHg.1(-1).min, P less than 0.02). Examination by light and electron microscopy demonstrated pulmonary capillary obstruction with hemolyzed erythrocyte (RBC) membranes with I-V infusion, but representative I-A animals did not demonstrate these findings. Conceivably, the systemic vascular bed filtered the fragmented RBC membranes in the I-A model, but this microvascular obstruction with altered RBCs and RBC fragments caused the pulmonary hypertension observed in the I-V infusion. We conclude that lactic acidosis does not increase pulmonary vascular tone in dogs, a finding compatible with most previous studies in which observed increases in PVR may be attributed to other effects from I-V acid infusion on circulating blood elements.     

Pressure in the pulmonary artery and transbronchial electroplethysmography in rats

A complex technique for pulmonary circulation study involving catheterization of pulmonary artery and transbronchial electroplethysmography has been tested in rats. The technique permits pulmonary artery pressure measurement and registration of electrical resistance in the lung lobe of closed-chest animals with the subsequent estimation of blood flow, blood volume and air content in the lungs expressed in adequate units per unit of organ volume. The experimental data characterizing standard values of the above parameters in rats are presented.     

Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive pressor drugs injection

The character and values of changes of the pulmonary and systemic hemodynamics following epinephrine, norepinephrine and angiotensin intravenous injection were studied in acute experiments on the anesthetized cats. After catecholamines injection pulmonary blood flow was always increased, meanwhile pulmonary artery pressure can be elevated (in the most observations) or decreased. In the cases of angiotensin administration the pulmonary blood flow could be augmented or decreased; pulmonary artery pressure had been increased or decreased independently from the character of changes of pulmonary flow. Thus, linear correlation between shifts of the pulmonary artery pressure and pulmonary blood flow had not been revealed. The changes of the pulmonary artery pressure were not correlated with the pulmonary vascular resistance ones; however they had strong relationship with the changes of the left atrial pressure. If the left atrial pressure was decreased the pulmonary artery pressure elevation was less, comparing with its values in experiments, where the left atrial pressure was increased; in the case of depressor shifts of pulmonary artery pressure, the left atrial pressure was also decreased. The character and values of the pulmonary blood flow changes were strongly correlated with the changes of the venous return; however they had no linear correlations with the right and left atrial pressures and pulmonary vascular resistance changes. Thus we concluded, that hemodynanics mechanisms of the pulmonary artery pressure and flow changes following vasoactive pressor drugs injection changes are different.     

Regulation of increase in anastomotic blood flow following pulmonary arterial occlusion

We have previously shown that there is an acute increase in anastomotic bronchial blood flow (Qbr) after pulmonary arterial obstruction in dogs. We examined the role of arachidonic acid metabolites in mediating this increase. The left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in open-chested anesthetized dogs (n = 19). Qbr was measured from the amount of blood that overflowed from the closed vascular circuit of the suspended LLL and changes in its weight. In the control animals, there was a prompt and significant increase in Qbr following pulmonary arterial obstruction. Pretreatment with indomethacin (n = 6) or sodium salicylate (n = 4) almost completely blocked this rise in Qbr. Following pulmonary arterial occlusion, there was a rise in both thromboxane and a prostacyclin metabolite (6-keto-PGF1 alpha) in the blood of the pulmonary circulation of the LLL, although the 6-keto-PGF1 alpha rose relatively more. Pretreatment with indomethacin caused a fall in both thromboxane and prostacyclin levels (n = 3), which no longer rose after pulmonary arterial occlusion. These findings suggested that the balance of the vasodilator (prostacyclin) and vasoconstrictor (thromboxane) prostaglandins may play an important role in mediating the rise in Qbr that follows pulmonary arterial obstruction.     

Reference cardiopulmonary values in normal dogs

The purpose of this project was to collate canine cardiopulmonary measurements from published and unpublished studies in our laboratory in 97 instrumented, unsedated, normovolemic dogs. Body weight; arterial and mixed-venous pH and blood gases; mean arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressures; cardiac output; heart rate; hemoglobin; and core temperature were measured. Body surface area; bicarbonate concentration; base deficit; cardiac index; stroke volume index, systemic and pulmonary vascular resistance indices; left and right cardiac work indices; alveolar partial pressure of oxygen (pO2) ; alveolar-arterial pO2 gradient (A-apO2); arterial, mixed-venous, and pulmonary capillary oxygen content; oxygen delivery; oxygen consumption; oxygen extraction; venous admixture; arterial and mixed-venous blood CO2 contents; and CO2 production were calculated. In the 97 normal, resting dogs, mean arterial and mixed-venous pH were 7.38 and 7.36, respectively; partial pressure of carbon dioxide (pCO2), 40.2 and 44.1 mm Hg, respectively; base-deficit, -2.1 and -1.9 mEq/liter, respectively; pO2, 99.5 and 49.3 mm Hg, respectively; oxygen content, 17.8 and 14.2 ml/dl, respectively; A-a pO2 was 6.3 mm Hg; and venous admixture was 3.6%. The mean arterial blood pressure (ABPm), mean pulmonary arterial blood pressure (PAPm), pulmonary artery occlusion pressure (PAOP) were 103, 14, and 5.5 mm Hg, respectively; heart rate was 87 beats/min; cardiac index (CI) was 4.42 liters/min/m2; systemic and pulmonary vascular resistances were 1931 and 194 dynes.sec.cm-5, respectively; oxygen delivery, consumption and extraction were 790 and 164 ml/min/m2 and 20.5%, respectively. This study represents a collation of cardiopulmonary values obtained from a large number of dogs (97) from a single laboratory using the same measurement techniques.     

Pulmonary diffusing capacity and capillary blood volume in aging dogs.

Single-breath carbon monoxide diffusing capacity (DLco), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) were measured in 24 beagle dogs aged 289-3,882 days. DLco and Vc were a function of age and alveolar volume (Va). Vc decreased with age resulting in changes in DLco. Changes in Vc may have been due to pulmonary morphological changes or to an exaggerated decrease in pulmonary blood flow in old dogs in response to 20-30 cmH-2O transpulmonary pressure. There was no age-related change in Dm.     

Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on experimentally induced air embolism in anesthetized dogs

We investigated the effects of OKY-046 and OKY-1580, thromboxane A₂(TxA₂) synthetase inhibitors, on plasma levels of 6-keto PGF_2α and TxB₂ in anesthetized dogs with experimentally induced air embolism.The percentage increase of tracheal pressure induced by room air infusion was suppressed significantly by premedication with OKY-046. The percentage increase of pulmonary artery blood pressure was suppressed significantly by premedication with OKY-046 compared to that in control group. By room air infusion after the premedication with OKY-046 and OKY-1580, systemic artery blood pressure did not show any significant changes. Plasma 6-keto PGF_2α level showed a marked increase by an intravenous infusion of room air, and such an increase became more predominant by the premedication with OKY-046 and OKY-1580. On the other hand,plasma TxB₂ level showed a marked increase by an intravenous infusion of room air, and such an increase became less predominant by the premedication with OKY-046 and OKY-1580. These results may suggest that OKY-046 and OKY-1580 are not only TxA₂ synthetase inhibitors but also PGI₂ synthetase accelerators and are useful drugs for treatment and prevention of thromboembolism.     

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.     

Pulmonary and systemic circulatory responses elicited by hyperosmotic solutions injected into the bronchial artery

In open chest anaesthetized dogs the haemodynamic effects of solutions of equal hyperosmolarity (viz. NaHCO3 8%, NaCl k.6%, and glucose 34.3%, solutions) given into the bronchial artery were studied. Administration of any of these solutions directly into the bronchial artery resulted in increased cardiac output, stroke volume, bronchial blood flow, and bronchial fraction of the cardiac output, and decreased heart rate and bronchial as well as pulmonary vascular resistances. When given into the pulmonary circulation, the same solutions evoked similar reactions of smaller magnitude. To exclude the effect of major surgical trauma and the open-chest condition, another experimental model closer to the physiological situation was also developed. In this preparation NaHCO3 failed to produce the above haemodynamic response even when given into the bronchial artery. After a one-hour bleeding period resulting in a drop of arterial blood pressure to 40 mmHg, while using the same preparation, the administration f NaHCO3 solution into the bronchial artery caused a significant rise in blood pressure in both the systemic and pulmonary arteries. In these experiments a correlation was found between arterial oxygen tension and the extent of change in blood pressure. The exact mechanism of action of the observed haemodynamic changes is still not clear. However, it is likely that receptors localized in the area of the bronchial circulation and sensitive to hypoxia might have played a role in the development of the haemodynamic effects described.     

The pulmonary hemodynamic changes under experimental myocardial ischemia in rabbits following beta-adrenoreceptors blockade

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied as well as in control animals and after the blockade of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular myocardial contractility, cardiac output and arterial pressure, decreased the pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary artery pressure decreased less than pulmonary artery blood flow as the result of elevating of the left atrial pressure, meanwhile pulmonary vascular resistance was not changed. Following myocardial ischemia in animals after the blockade of the beta-adrenoreceptors, the pulmonary flow decreased the same as in control animals. However, the pulmonary artery pressure was decreased twofold more significantly than in control animals, and its diminishing was in the same degree as the pulmonary artery flow. Following myocardial ischemia after the blockade of the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the left atrial pressure did not change significantly because the myocardial contractility decreased less than in control animals.