Jay J. Williams

Influence of isoflurane on hypoxic pulmonary vasoconstriction in dogs

The authors studied the influence of locally administered isoflurane anesthesia on the pulmonary vascular response to regional alveolar hypoxia (hypoxic pulmonary vasoconstriction [HPV]) over a range of cardiac outputs (COs) in seven mechanically ventilated, closed-chest dogs. The right lung was ventilated with 100% O2 throughout the study. The left lung was ventilated with either 100% O2 (normoxia) or an hypoxic gas mixture (hypoxia). Different alveolar concentrations of isoflurane (0, 1, and 2.5 MAC) were administered to the left lung in a randomized sequence. The CO was altered by opening and closing surgically produced arteriovenous fistulae, at all isoflurane concentrations, and by hemorrhage at 0 MAC isoflurane. The magnitude of the HPV response was measured by differential CO2 elimination in the absence of isoflurane and by venous admixtures in all phases. During normoxia, the left lung effective flow (&OV0422;L%) measured from differential CO2 excretion was 39.9 ± 1.2% of the total blood flow and decreased to 18.8 ± 2.6% when ventilated with the hypoxic gas mixture. Venous admixture (&OV0422;VA/&OV0422;T%) was significantly correlated with &OV0422;L% during hypoxic ventilation in the absence of isoflurane. &OV0422;VA/&OV0422;T% was 22.3 ± 2.7% during hypoxia with normal CO, and it increased significantly to 27.7 ± 1.1% when the CO was increased 43%. It was not significantly altered (23.6 ± 3.6%) when the CO was decreased by 54%. Isoflurane 2.5 MAC significantly increased &OV0422;VA/QT% during hypoxic ventilation of the left lung to 33.9 ± 2.6% with low CO and 35.4 ± 1.7% with normal CO. Isoflurane 1 MAC increased &OV0422;VA/QT% to 27.2 ± 2.7% with normal CO and 28.1 ± 2.6% with high CO. Comparing the effects of the different concentrations of isoflurane on &OV0422;VA/&OV0422;T% during left lung hypoxia under the same conditions of CO, mixed venous and alveolar oxygen tension, and pulmonary artery and pulmonary artery occlusion pressures revealed a significant direct effect of isoflurane dose such that: (% depression of HPV) = [22.8(% alveolar isoflurane) – 5.3]. The ED50 for this response was 2.4% alveolar isoflurane. The authors conclude that isoflurane directly depresses HPV and that secondary influences of the anesthetic action should be considered in the interpretation of the action of inhalational agents on this response in vivo.

ED50 of Alfentanil for Induction of Anesthesia in Unpremedicated Young Adults

This study determined the ED50 and ED90 of alfentanil for unconsciousness and anesthesia. A bolus of alfentanil was given to 28 healthy unpremedicated adults undergoing gynecologic or orthopedic procedures in one of four dosages: 100, 150, 200, or 250 μg/kg. Three indicators of induction were assessed 90 s later: eyelid reflex, response to verbal commands to breathe, and response to placement of a nasopharyngeal airway. Succinylcholine, given at 90 s, was followed by tracheal intubation 1 min later. From probit analysis, the ED50 and ED90 for loss of voice response were 92 and 111 μg/kg, respectively, and for loss of nasopharyngeal airway response, 111 and 169 μg/kg. A high incidence of chest wall rigidity (75%) and movements of the limbs (54%) or eyes (25%) was seen. There were statistically significant increases of the heart rate prior to stimulation and of both the heart rate (21% rise) and systolic blood pressure (10% rise) from control to the peak value following intubation. Differences between alfentanil doses were not significant. Naloxone was required in 36% of patients for end-tidal PCO2 greater than 48 mmHg at emergence from anesthesia; no patient required additional naloxone. Nausea or vomiting occurred in 39% of all subjects. Two patients recalled placement of the nasopharyngeal airway. We conclude that alfentanil is an anesthetic, and its ED50 (analogous to MAC of inhalational agents) is 111 μg/kg. The blood pressure and heart rate responses to laryngoscopy and intubation were modest after doses that allowed for extubation as early as 51 min after induction.

Time Course and Responses of Sustained Hypoxic Pulmonary Vasoconstriction in the Dog

The stability of the pulmonary blood pressure and flow response to alveolar hypoxia (hypoxic pulmonary vasoconstriction or HPV) was studied in six pentobarbital anesthetized, mechanically ventilated open-chested dogs. Aortic and left pulmonary artery blood flows; systemic and pulmonary arterial, central venous, left atrial, and airway pressures; hemoglobin; arterial and mixed venous blood gases were measured. The right lung was ventilated continuously with 100% oxygen, while the left lung was ventilated alternately with 100% O2 (prehypoxia control phase), an hypoxic gas mixture containing 4% O2, 3% CO2, balance N2 for 4 h, or 100% O2 (post-hypoxia control phase). Hypoxic ventilation of the left lung resulted in an immediate and sustained decrease in left lung blood flow (&OV0422;L%) from 39.0 ± 1.8% (mean ± SE) to 9.9 ± 3.6% at 15 min of hypoxic ventilation. &OV0422;L% remained decreased and did not vary significantly during the 4 h of hypoxia. Venous admixture correspondingly was increased and Pao2 decreased by hypoxic ventilation and did not vary significantly during the 4 h of hypoxia. All variables returned to control levels upon reestablishing ventilation with 100% O2.While the maximal reduction in &OV0422;L% with left lung hypoxic ventilation was identical to that observed during atelectasis previously in our laboratory, the time course of the response was different. The response to hypoxia was maximal by 15 min, however, &OV0422;L% decreased more slowly during atelectasis, where the maximal reduction was observed by 60 min. The present study therefore demonstrated that hypoxic ventilation of the left lung yielded an immediate and sustained decrease in left lung blood flow for 4 h. The stability of the HPV response probably was accounted for by the lack of such confounding factors as respiratory alkalosis, severe systemic hypoxemia, and increased cardiac output.

Hypoxic Pulmonary Vasoconstriction Is Not Potentiated by Repeated Intermittent Hypoxia in Closed Chest Dogs

Hypoxic pulmonary vasoconstrictor (HPV) responses were measured with repeated intermittent hypoxic challenges in eight non-traumatized closed chest dogs anesthetized with pentobarbital. The right lung was ventilated continuously with 100% O2 while the left lung was either ventilated with 100% O2 (control) or ventilated with a gas mixture containing 3–4% O2 (hypoxia). Mean per cent left lung blood flow for all four normoxic periods was 43.1 ± 1.5% (mean ± SE) of the total blood flow by the SF6 excretion method and 40.8 ± 1.1% by the differential CO2 excretion method, corrected for the Haldane effect. With hypoxic ventilation, flow diversion from the hypoxic lung was maximal with the first exposure and did not change subsequently with a total of four alternating exposures to normoxia and hypoxia. Flow diversion during hypoxia was approximately 50.5 ± 2.4% by the SF6 method and 50.3 ± 3.5% by the Vco2 method. This result contrasts with the increasing flow diversion response with intermittant hypoxic exposure that has been reported in animals exposed first to thoracotomy and surgical dissection. It is concluded that in the absence of surgical trauma the initial response to hypoxia is maximal and is not potentiated by repeated hypoxic stimulation.

The effect of pleural pressure on the hypoxic pulmonary vasoconstrictor response in closed chest dogs.

The effect of intrapleural pressure on the hypoxic pulmonary vasoconstrictor (HPV) responses to atelectasis and hypoxia were measured in two groups of anesthetized closed chest dogs. The right lung was continuously ventilated with 100% O2. The left lung was initially ventilated with 100% O2, (hyperoxia) but subsequently underwent either reabsorption atelectasis (atelectasis; group I) or ventilation with a hypoxic gas mixture (hypoxia; group II). The mean intrapleural pressure in the left hemithorax was 5.4 cm H2O during hyperoxia, but with left lung atelectasis decreased significantly to −3.8 cm H2O by 15 minutes and to −4.2 cm H2O by 90 minutes. Venous admixture (%VA) increased significantly from 10.3% during hyperoxia to 33.2% at 15 minutes of left lung atelectasis and to 34.6% at 90 minutes. However, after sternotomy with the left lung still atelectatic, the %VA decreased significantly to 25.4%. For the hypoxia group, %VA increased significantly from 9.2% during hyperoxia to 29.9% at 15 minutes of left lung hypoxia and 25.1 % at 90 minutes. HPV diverted blood flow away from both atelectatic lung and hypoxic lung. However, due to the negative intrapleural pressure generated during left lung resorption atelectasis when the chest was closed, HPV was less effective during atelectasis than during hypoxia.

Pulmonary capillary permeability in man and a canine model of chemical pulmonary edema.

Abstract Pulmonary capillary permeability-surface products (PSP) for sucrose and water have been calculated in normal, awake man and in anesthetized dogs using multiple indicator dilution data and a numerical deconvolution technique to estimate maximal extraction. In man and control animals the PSP for sucrose was found to be 9.1 and 7.1 cm 3 /sec, respectively, while PSPs for water were found to be 34.0 and 30.9 cm 3 /sec. The effects of flow and choice of the reference tracer (red blood cells or albumin) were examined. With the exception of water in man, the PSPs for sucrose and water did not change significantly with an increased cardiac output, regardless of the reference tracer chosen. Pulmonary capillary damage induced by the infusion of 75 mg/kg of alloxan in dogs increased the PSPs for sucrose and water by 35 and 52%, respectively, when red cells formed the reference tracer material. This change was eliminated for sucrose when albumin formed the reference tracer and reduced the magnitude of the change for water from 52 to 34%. The permeability increases in the alloxan damaged dogs occurred in the presence of normal pulmonary artery and wedge pressures. We conclude that the exchange of water is not flow-limited at physiologic or higher rates of perfusion and that albumin is misleading as a reference tracer in multiple indicator dilution studies of pulmonary edema.

Influence of the method of re-expansion of atelectatic lung upon the development of pulmonary edema in dogs.

An endobronchial tube was used to separately ventilate each lung in anesthetized dogs, and absorption atelectasis was then induced in the left lung and maintained for 3 1/2 h. The left lung was partially re-expanded by ventilation at normal tidal volumes for 10 min, and then completely re-expanded by manual hyperinflation. This delayed re-expansion was associated with an extravascular water content significantly greater than that of the right lung. A previous study demonstrated no increase in the ratio of left to right lung water content after 3 h of atelectasis alone and a significant increase after immediate hyperinflation. Delayed re-expansion produces significantly different results, and it is therefore concluded that the method of lung re-expansion influences the development of pulmonary edema after atelectasis