Increased pulmonary perfusion worsens ventilation-perfusion matching.

BACKGROUND: Severe exercise and administration of vasopressors may adversely affect pulmonary gas exchange in humans. The role of increases in pulmonary perfusion in worsening ventilation-perfusion (VA/Q) relationships is unclear, however, because concomitant changes in ventilation and alveolar gas composition occur. The purpose of this study was to determine whether increasing of lobar blood flow increased VA/Q heterogeneity in the absence of changes in respiratory parameters. METHODS: Six pentobarbital-anesthetized dogs underwent bilateral thoracotomies, left upper lobectomy, and placement of an electromagnetic flow probe on the left lower lobe (LLL) pulmonary artery, and catheters were inserted into the LLL pulmonary artery distal to the flow probe and confluent trunk of the LLL pulmonary vein. A bronchial divider was inserted to allow separate ventilation of the right lung and LLL. Blood flow to the LLL (QLLL) was increased in random order to two and three times baseline blood flow by opening an arteriovenous fistula and partially occluding the right pulmonary artery. Minute ventilation and alveolar PCO2 of the lobe were unchanged due to use of constant tidal volume and respiratory rate and inspiration of variable amounts of carbon dioxide. VA/Q distributions of the LLL were obtained using the multiple inert gas elimination technique. The tracer inert gas arterial-alveolar difference ([a-A]D) area was used to assess VA/Q mismatch. RESULTS: Increasing QLLL increased mean pulmonary artery pressure in the LLL (LLL Ppa). The PO2 of the LLL pulmonary venous blood remained unchanged, as the mixed venous oxygen tension (PvO2) was markedly increased. VA/Q inequality was increased, indicated by a 40% increase in the [a-A]D area when QLLL was increased to two times greater than baseline QLLL and a 58% increase in the [a-A]D area with three times greater than baseline QLLL. The [a-A]D area was highly correlated with the lobar blood flow (r = 0.97) and LLL Ppa (r = 0.97). CONCLUSIONS: Marked increases in lobar blood flow and Ppa worsened pulmonary gas exchange. The degree of impairment was correlated with the degree of increase in lobar perfusion. However, increased lobar perfusion did not affect LLL pulmonary venous blood oxygenation because the decrease in PO2, due to increased VA/Q mismatch, was opposed by an increase in PO2, due to increased PvO2.

Effect of inspired CO2 on ventilation and perfusion heterogeneity in hyperventilated dogs.

We studied the effect of inspired CO2 on ventilation-perfusion (VA/Q) heterogeneity in dogs hyperventilated under two different tidal volume (VT) and respiratory rate conditions with the use of the multiple inert gas elimination technique. Dogs anesthetized with pentobarbital sodium were hyperventilated with an inspired fraction of O2 of 0.21 by using an increased VT (VT = 30 ml/kg at 18 breaths/min) or an increased respiratory rate (VT = 18 ml/kg at 35 breaths/min). The arterial CO2 tension (PaCO2) was varied to three levels (20, 35, and 52 Torr) by altering the inspired PCO2. The orders of type of ventilation and PaCO2 level were randomized. Compared with normocapnia, VA/Q heterogeneity was increased during hypocapnia induced by increased respiratory rate ventilation, which was indicated by an increase in dispersion indexes and arterial-alveolar inert gas partial pressure difference areas (P < 0.01). In contrast, VA/Q heterogeneity was not affected by hypocapnia when a large VT ventilation was used. Under the conditions of our study, hypercapnia did not result in statistically significant changes in VA/Q heterogeneity with either type of ventilation. Increased VT ventilation reduced dead space at all PaCO2 levels (P < 0.01) and reduced the log standard deviation of the ventilation distribution during normocapnia (P < 0.05) and hypocapnia (P < 0.01). We conclude that hypocapnia increased VA/Q heterogeneity when hyperventilation was achieved with a rapid respiratory rate. Therefore, a lack of improvement in VA/Q matching with inhaled CO2 may be associated with the use of a large VT. These data suggest that hypocapnic bronchoconstriction may be important in mediating hypocapnia-induced VA/Q inequality in dogs.

Hypocapnia worsens arterial blood oxygenation and increases VA/Q heterogeneity in canine pulmonary edema.

BACKGROUND: Hyperventilation frequently is employed to reduce carbon dioxide partial pressure in patients in the operating room and intensive care unit. However the effect of hypocapnia on oxygenation is complex and may result in worsening in patients with preexisting intrapulmonary shunt. To better define the interplay between hypocapnia and oxygenation, the effects of hypocapnia and hypercapnia on the matching of ventilation (VA) and perfusion (Q) were studied in dogs with oleic acid-induced pulmonary edema, using the multiple inert gas elimination technique. METHODS: Eight pentobarbital-anesthetized, closed-chested dogs were administered 0.06 ml/kg of oleic acid at least 150 min prior to study. Ventilation was set with an FIO2 of 0.90, a tidal volume of 20 ml/kg, and a respiratory rate of 35 breaths/min. The arterial carbon dioxide tension (PaCO2) was varied in a randomized order to three levels (26, 38, and 50 mmHg) by altering the amount of CO2 in the inspired gas mixture. Gas exchange was assessed by true shunt, dead space, the log standard deviation of the perfusion (log SDQ) and the ventilation (log SDV) distributions, and the tracer inert gas arterial-alveolar difference ([a-A]D) area. RESULTS: Cardiac output (4.1 +/- 0.4 L/min), mean pulmonary artery pressure (25 +/- 1 mmHg), inert gas shunt (22 +/- 3%), and dead space (38 +/- 4%) during normocapnia were not different from that during hypocapnia and hypercapnia. Hypocapnia increased (P < .05) the alveolar-arterial oxygen tension difference (P[A-a]O2) and decreased (P < .05) the arterial blood oxygen tension (PaO2, 181 +/- 33 mmHg vs. 221 +/- 35 mmHg with normocapnia). P[A-a]O2 and PaO2 were unaffected by hypercapnia. During hypocapnia, VA/Q inequality increased, demonstrated by an increase (P < .05) in log SDQ (1.60 +/- 0.15 vs. 1.35 +/- 0.19 with normocapnia) and in the [a-A]D area (0.63 +/- 0.09 vs. 0.50 +/- 0.09 with normocapnia) indexes of VA/Q heterogeneity. During hypercapnia, the [a-A]D area (0.63 +/- 0.11) and log SDV (1.13 +/- 0.10 compared to 0.97 +/- 0.12 with normocapnia) also were increased (P < .05). With hypocapnia, there was a small but insignificant increase in blood flow to shunt and low VA/Q areas (29 +/- 4% compared to 26 +/- 4% with normocapnia). In the presence of a high FIO2, this small increase in shunt and low VA/Q may result in a significant decrease in PaO2. CONCLUSIONS: Both hypocapnia and hypercapnia were associated with an increased VA/Q inequality. However, PaO2 decreased and P[A-a]O2 increased with only hypocapnia. These results suggest that hyperventilation to reduce PaCO2 may be detrimental to arterial PO2 in some patients with lung disease.

Effect of regional alveolar hypoxia on gas exchange in pulmonary edema.

We studied the effects of left lower lobe (LLL) alveolar hypoxia on ventilation-perfusion (VA/Q) heterogeneity in anesthetized dogs with acute (1-h-old) and mature (24-h-old) permeability pulmonary edema, induced by intravenous administration of 0.05 ml/kg of oleic acid. The left upper lobe was removed and a bronchial divider was placed to allow separate ventilation of the right lung (fraction of inspired oxygen [FIO2] = 1.0) and the LLL (FIO2 = 1.0 or 0.05). Gas exchange was assessed using the multiple inert gas elimination technique. In acute pulmonary edema, LLL hypoxia reduced LLL blood flow and increased true shunt of the LLL compared with a hyperoxic control group. VA/Q heterogeneity of the LLL was markedly increased, indicated by increases in the logarithmic standard deviation of the perfusion distribution (log SDQ) and the retention index of dispersion corrected for shunt (DISPR*). Increases in true shunt and log SDQ were significantly greater than those observed with lobar hypoxia in normal lungs before oleic acid injury. In mature oleic acid injury, LLL alveolar hypoxia resulted in a similar reduction in LLL blood flow and increase in inert gas shunt and DISPR*. We conclude that lobar alveolar hypoxia increased VA/Q heterogeneity of the hypoxic lobe to a greater degree in oleic acid-induced pulmonary edema compared with normal lungs. Phase of oleic acid injury (acute versus mature) did not affect gas exchange during alveolar hypoxia.

Pulmonary blood flow and ventilation-perfusion heterogeneity.

We studied the independent influence of changes in perfusion on pulmonary gas exchange in the left lower lobe (LLL) of anesthetized dogs. Blood flow to the LLL (QLLL) was raised 50% (increased QLLL) or reduced 50% (decreased QLLL) from baseline by partial occlusion of the right or left pulmonary artery, respectively. Minute ventilation and alveolar PCO2 of the LLL remained constant throughout the study. We determined ventilation-perfusion distributions of the LLL using the multiple inert gas elimination technique. Increased QLLL impaired LLL pulmonary gas exchange. All dispersion indexes and all arterial-alveolar difference areas increased (P less than 0.01). Decreased QLLL increased the log standard deviation of the perfusion distribution (P less than 0.05) and reduced the log standard deviation of the ventilation distribution (P less than 0.01) but did not affect the dispersion indexes or alveolar-arterial difference areas. We conclude that ventilation-perfusion heterogeneity is increased by independent changes in perfusion from normal baseline blood flow, even when ventilation and alveolar gas composition remain constant.

Lack of alveolar O2 during lung reperfusion does not decrease edema formation.

We previously reported that pulmonary arterial occlusion for 48 h followed by 4 h of reperfusion in awake dogs results in marked edema and inflammatory infiltrates in both reperfused and contralateral lungs (Am. Rev. Respir. Dis. 134: 752-756, 1986; J. Appl. Physiol. 63: 942-950, 1987). In this experiment we study the effects of alveolar hypoxia on this injury. Anesthetized dogs underwent thoracotomy and occlusion of the left pulmonary artery. Twenty-four hours later the dogs were reanesthetized, and a double-lumen endotracheal tube was placed. The right lung was continuously ventilated with an inspiratory O2 fraction (FIO2) of 0.35. In seven study animals the left lung was ventilated with an FIO2 of 0 for 3 h after the left pulmonary artery occluder was removed. In six control animals the left lung was ventilated with an FIO2 of 0.35 during the same reperfusion period. Postmortem bloodless wet-to-dry weight ratios were 5.87 +/- 0.20 for the left lower lobe and 5.32 +/- 0.12 for the right lower lobe in the dogs with hypoxic ventilation (P less than 0.05 for right vs. left lobes). These values were not significantly different from the control dog lung values of 5.94 +/- 0.22 for the left lower lobe and 5.11 +/- 0.07 for the right lower lobe (P less than 0.05 for right vs. left lobes). All values were significantly higher than our laboratory normal of 4.71 +/- 0.06. We conclude that reperfusion injury is unaffected by alveolar hypoxia during the reperfusion phase.

Effect of regional alveolar hypoxia on gas exchange in dogs.

We studied the effects of left lower lobe (LLL) alveolar hypoxia on pulmonary gas exchange in anesthetized dogs using the multiple inert gas elimination technique (MIGET). The left upper lobe was removed, and a bronchial divider was placed. The right lung (RL) was continuously ventilated with 100% O2, and the LLL was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Whole lung and individual LLL and RL ventilation-perfusion (VA/Q) distributions were determined. LLL hypoxia reduced LLL blood flow and increased the perfusion-related indexes of VA/Q heterogeneity, such as the log standard deviation of the perfusion distribution (log SDQ), the retention component of the arterial-alveolar difference area [R(a-A)D], and the retention dispersion index (DISPR*) of the LLL. LLL hypoxia increased blood flow to the RL and reduced the VA/Q heterogeneity of the RL, indicated by significant reductions in log SDQ, R(a-A)D, and DISPR*. In contrast, LLL hypoxia had little effect on gas exchange of the lung when evaluated as a whole. We conclude that flow diversion induced by regional alveolar hypoxia preserves matching of ventilation to perfusion in the whole lung by increasing gas exchange heterogeneity of the hypoxic region and reducing heterogeneity in the normoxic lung.

Regional alveolar hypoxia does not affect air embolism-induced pulmonary edema.

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema resulting from venous air embolization. Anesthetized dogs had the left upper lobe removed and a double-lumen tube placed so that right lung and left lower lobe (LLL) could be ventilated independently. Air was infused into the femoral vein for 1 h during bilateral ventilation at an inspiratory O2 fraction (FIO2) of 1.0. After cessation of air infusion the LLL was then ventilated with a hypoxic gas mixture (FIO2 = 0.05) in six animals and an FIO2 of 1.0 in six other animals. Lung hydroxyproline content was measured as an index of lung dry weight. LLL bloodless lobar wet weight-to-hydroxyproline ratio was 0.33 +/- 0.06 mg/micrograms in the animals exposed to LLL hypoxia and 0.37 +/- 0.03 mg/micrograms (NS) in the animals that had a LLL FIO2 of 1. Both values were significantly higher than our laboratory normal values of 0.19 +/- 0.01 mg/micrograms. We subsequently found in four more dogs exposed to global alveolar hypoxia before and after air embolism that the air injury itself significantly depressed the hypoxic vasoconstrictor response. We conclude that regional alveolar hypoxia has no effect on pulmonary edema formation due to air embolism. The most likely reason for these findings is that the air embolism injury itself interfered with hypoxic pulmonary vasoconstriction.

Alveolar hypoxia, inhibition of hypoxic pulmonary vasoconstriction, and permeability edema.

We previously reported that regional alveolar hypoxia reduces oleic acid-induced permeability edema formation [Cheney et al. (1987). J. Appl. Physiol. 62: 1690-1697]. In order to define the role of hypoxic pulmonary vasoconstriction (HPV) on this effect, we studied the effects of regional alveolar hypoxia on permeability edema formation with this response inhibited. Dogs weighing 25 +/- 1 kg in which the HPV response had been inhibited by the administration of minoxidil (1 mg/kg i.v.) were anesthetized, mechanically ventilated and had a bronchial divider placed so the left lower lobe (LLL) could be ventilated with an FIO2 = 0.05 or FIO2 = 1, while the right lung was continuously ventilated with an FIO2 = 1.0. In 10 study animals the LLL was ventilated with an FIO2 = 0.05 for 4 h after induction of bilateral permeability pulmonary edema with 0.05 ml/kg of intravenous oleic acid. In six control animals the LLL was ventilated with an FIO2 = 1 for 4 h after the same injury. Postmortem gravimetric analysis indicates that alveolar hypoxia of the LLL with the HPV response inhibited had no effect on pulmonary edema formation. We conclude that inhibition of HPV abolishes the protective effect of regional alveolar hypoxia on oleic acid-induced permeability edema formation.

Effect of regional alveolar hypoxia on permeability pulmonary edema formation in dogs.

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema formation. Anesthetized dogs had a bronchial divider placed so that the left lower lobe (LLL) could be ventilated with a hypoxic gas mixture (HGM) while the right lung was continuously ventilated with 100% O2. Bilateral permeability edema was induced with 0.05 ml/kg oleic acid and after 4 h of LLL ventilation with an HGM (n = 9) LLL gross weight was 161 +/- 13 (SE) g compared with 204 +/- 13 (SE) g (P less than 0.05) in the right lower lobe (RLL). Bloodless lobar water and dry weight were also significantly lower in the LLL as compared with the RLL of the study animals. In seven control animals in which the LLL fractional inspired concentration of O2 (FIO2) was 1.0 during permeability edema, there were no differences in gravimetric variables between LLL and RLL. In eight additional animals, pulmonary capillary pressure (Pc), measured by simultaneous occlusion of left pulmonary artery and vein, was not significantly different between LLL FIO2 of 1.0 and 0.05 either before or after pulmonary edema. We conclude that, in the presence of permeability pulmonary edema, regional alveolar hypoxia causes reduction in edema formation. The decreased edema formation during alveolar hypoxia is not due to a reduction in Pc.

Hypoxic pulmonary vasoconstriction does not affect hydrostatic pulmonary edema formation.

We studied the effects of regional hypoxic pulmonary vasoconstriction (HPV) on lobar flow diversion in the presence of hydrostatic pulmonary edema. Ten anesthetized dogs with the left lower lobe (LLL) suspended in a net for continuous weighing were ventilated with a bronchial divider so the LLL could be ventilated with either 100% O2 or a hypoxic gas mixture (90% N2-5% CO2-5% O2). A balloon was inflated in the left atrium until hydrostatic pulmonary edema occurred, as evidenced by a continuous increase in LLL weight. Left lower lobe flow (QLLL) was measured by electromagnetic flow meter and cardiac output (QT) by thermal dilution. At a left atrial pressure of 30 +/- 5 mmHg, ventilation of the LLL with the hypoxic gas mixture caused QLLL/QT to decrease from 17 +/- 4 to 11 +/- 3% (P less than 0.05), pulmonary arterial pressure to increase from 35 +/- 5 to 37 +/- 6 mmHg (P less than 0.05), and no significant change in rate of LLL weight gain. Gravimetric confirmation of our results was provided by experiments in four animals where the LLL was ventilated with an hypoxic gas mixture for 2 h while the right lung was ventilated with 100% O2. In these animals there was no difference in bloodless lung water between the LLL and right lower lobe. We conclude that in the presence of left atrial pressures high enough to cause hydrostatic pulmonary edema, HPV causes significant flow diversion from an hypoxic lobe but the decrease in flow does not affect edema formation.

Coronary, collateral, and perfusion territory responses to aortic banding.

The objectives of this study were 1) to separate anatomic from functional variables causing the increased minimal coronary resistance seen with hypertrophy; 2) to investigate whether increased intraluminal pressure and tangential wall stress lead to collateral proliferation; 3) to define changes in vascular perfusion territories resulting from hypertrophy. Coronary and collateral resistances of the four coronary arteries were determined in empty, beating hearts from 10 control dogs and 11 dogs with myocardial hypertrophy produced by 4 wk of aortic banding. In hypertrophied hearts the coronary flow per gram at 100 mmHg and the slope of the pressure-flow line were significantly decreased. Coronary flow-to-body weight ratios were not different; thus the decreased flow per gram tissue with hypertrophy was due to increased tissue mass rather than changes in vascular resistance. Collateral flows were similar for both groups, indicating that increased pressure and wall stress did not cause significant collateral growth. Both ventricles hypertrophied and all vascular beds were equally affected, but distribution of the increased mass varied for different vascular beds.

Silicone rubber applied within the eye: a preliminary study.

Clear, room temperature vulcanizing silicone rubber (RTV) has already been shown to have well-defined optical and mechanical properties that allow its use as an active optical element. In this work RTV is considered as a possible material for substitution of damaged and/or diseased parts of the human eye, such as the cornea and crystalline lens. The interaction of cured and uncured RTV with eye tissue and eyelike tissue was investigated, and the results support the use of this material in the eye.