Biomedical subjects
Publications and source records attributed to M Manohar.
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A technique was developed for long-term catheterization of the coronary sinus in calves and ponies. A catheter with a 10 to 12 cm-long stiff segment was implanted via right lateral thoracotomy. Catheters were kept patent up to 10 weeks after the surgical procedure. At that time, location of the catheter tip was confirmed both by determining oxygen tension of the anaerobically sampled blood and by radiography. Base-line values of oxygen venous blood of non-anesthetized calves and ponies are reported.
A technique was developed for the implantation of an electromagnetic flow probe and vascular occluder onto the right and left coronary arteries in the calf and pony. Surgical manipulation was well tolerated in the animals. The subcutaneous housing on the peripheral ends of these devices of the lateral thoracic wall served as a maintenance-free technique for chronic exteriorization of these devices. Implantation onto the coronary arteries required a surgical technique which accomplished the prerequisites for proper flow probe function. A reactive hyperemic response was elicited in each animal by implanting an inflatable vascular occluder distal to the flow probe. The correct function of these devices postoperatively established the feasibility of this surgical technique for implanting these devices on the coronary arteries for chronic studies of coronary circulation.
Dopamine (DA) given IV by bolus injection (5, 10, 20 micrograms/kg) and by slow IV infusion (20 micrograms . kg . min) depressed VE significantly in awake normoxic goats. These responses were attenuated but not eliminated during hypoxia (FIO2 = 0.14) and hyperoxia (FIO2 = 1.0). After administering haloperidol (0.3 mg/kg) or removing the carotid bodies (CBE) there was greater attenuation of the response to DA. In normal goats haloperidol also caused a significant increase in ventilatory response to acute hypoxia and exaggerated depression of VE after 3--5 breaths O2 during steady-state hypoxia. After CBE haloperidol caused mild hypoventilation (delta PaCO2 = +2.5 Torr). CBE induced hypoventilation in goats (delta PaCO2 = +7.8 Torr) and reduced, but did not totally eliminate, peripheral chemoreceptor responses to acute stimuli (NaCN injection, transient N2 and transient O2 breathing). Attempted aortic body denervation did not eliminate these residual responses. We conclude: (1) DA may function as a modulator of carotid body (CB) function in the goat, (2) there may be central excitatory DA receptors in the goat, (3) the CB is important in regulating resting ventilation in the goat.
Plasma and lung lymph beta-glucuronidase and aryl sulfatase A specific activity were measured before and for 48 hours after a 50% full-thickness burn in the adult sheep. We noted a significant increase in plasma activity of both enzymes with maximum increase occurring 3 hours postburn, with levels returning toward baseline at 48 hours. Increase in plasma activity correlated in time course with increases in pulmonary vascular resistance. Lung lymph specific activity increased to levels identical to that in plasma but the time course lagged behind by 1 to 3 hours.
The measurement of pulmonary vascular pressure and plasma oncotic pressure (pi p) is reported to be useful for predicting excess fluid transport across the pulmonary microcirculation in the critically ill. However, interpretation of change in these forces must take into consideration the compensatory changes in the other Starling forces, particularly interstitial oncotic pressure (pi i) and the permeability characteristics of the membrane. We calculated pulmonary microvascular pressure Pmv, pi p, and pi i in unanesthetized sheep with lung lymph fistulae. We altered Pmv by fluid loading and pi p by producing a severe hypoproteinemia after hemorrhagic shock and altered the membrane with endotoxin. We compared these with changes in the pulmonary transvascular fluid filtration rate (Qf). We found Pmv correlated very well with Qf during volume loading and during the post-shock hypoproteinemic state. pi i decreased in response to decreases in pi p, producing a relatively constant oncotic gradient (pi p-pi i). pi p then correlated very poorly with Qf when hypoproteinemia was present. There was essentially no correlation between any of the pressures and Qf after the severe permeability change produced by endotoxin.
The colloid osmotic pressure of plasma, pi p, and lung lymph pi i, in the adult sheep was measured with a membrane osmometer and calculated from the protein content using the Landis and Pappenheimer equation. Measured (M) plasma oncotic pressure was 6 mm Hg lower than calculated (C), for normal sheep plasma. The difference between (M) and (C) decreased as protein content decreased. The (M) lymph value, considered to be equal to interstitial fluid, was only 1 mm Hg lower than (C) for normal lymph. This resulted in a difference between the calculated and measured oncotic gradient (pi p-pi i) of nearly 5 mm Hg. This difference decreased as protein content decreased in plasma and lymph. The difference between measured and calculated values may in part be explained by the differences in A/G ratio between human and sheep plasma and between sheep plasma and lymph. Measured oncotic pressure in plasma and lymph after severe hemorrhagic and endotoxic shock did not differ significantly from that in the normal animal.
We compared the response of the pulmonary microcirculation to fluid overload before and 24 hours after hemorrhagic shock, resuscitated with either blood or crystalloid, to determine whether vascular permeability was altered, making the lung more susceptable to fluid overload after shock and whether this response differed depending on the type of resuscitation fluid. Fourteen unanesthetized sheep with chronic lung lymph fistula were given a fluid challenge (one half of blood volume) before and 24 hours after hemorrhagic shock. Seven sheep were resuscitated after whock with shed blood and seven sheep were resuscitated with Ringer's lactate alone equal to 2.5 times the amount of shed blood. Pulmonary vascular pressures and lung lymph flow Ql were at baseline in both groups 24 hours after resuscitation except for the decreased plasma oncotic pressure pi p in the crystalloid group. Interstitial oncotic pressure, pi i was also lowered in this group such that the gradient (pi p-pi i) remained at baseline. In the blood group, pulmonary vascular pressures and QL increased transiently after fluid loading before and after shock with the mean time for QL to return to baseline being 5.5 and 5.9 hours for the preshock and postshock periods, respectively. In the crystalloid group, fluid loading after shock produced an increase in pulmonary vascular pressures resulting in a significant increase in QL over the preshock fluid response with the mean time for QL to return to baseline being 10.1 hours. However, changes in the value of (pi p-pi i) were identical to those seen before shock. Therefore we noted that 24 hours after shock, lung permeability was not significantly altered but crystalloid resuscitation did make the lung more susceptible to volume overload.
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Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.
Plasma oncotic pressure is considered to be an important factor in controlling lung water after hemorrhagic shock. However, it is the gradient between plasma and interstitial oncotic pressure which affects the pulmonary transvascular fluid filtration rate, Qf. Our objective was to determine the effect of decreasing plasma oncotic pressure, pip, on Qf, on interstitial oncotic pressure pii, and on the oncotic gradient. Chronic lung lymph fistulas were created in 16 sheep. Lymph flow, a reliable index of Qf, plasma and lymph (equal to interstitial) oncotic pressures, and vascular pressures were monitored in unanesthetized sheep, before and during hemorrhagic shock (50% blood volume), during resuscitation (3 hours), and during recovery (24 hours). Resuscitation was either with shed blood or lactated Ringer's solution in sufficient quantity to return left atrial pressure and cardiac output to baseline levels. During resuscitation with blood, lymph flow increased by 115%. The pip remained constant, while pii decreased, increasing the oncotic gradient. Crystalloid resuscitation produced on increase in lymph flow equal to that in the blood group at 120% over baseline; however, pip decreased by 50%, producing an oncotic gradient 4 mm Hg less than that of blood group. This was not reflected by a difference in Qf between the groups. During recovery Qf returned to baseline in the blood group and in most of the crystalloid group, as the oncotic gradient returned to baseline, despite a significant decrease in pip due to a compensatory decrease in pii. We conclude that during resuscitation Qf does not appear to be increased by a decrease in the oncotic gradient. During recovery a major decrease in pip can be compensated for rapidly by a decrease in pii, leading to no change in interstitial fluid content.
Hemodynamics, myocardial function, and regional myocardial blood flow (MBF) were measured in 6 closed-chest ponies anesthetized with ketamine hydrochloride before (control) and after creation of acute right ventricular systolic hypertension (RVSH) during normoxia and isocapnic hypoxia. The right ventricular (RV) systolic pressure during each RVSH approached 90 mmHg. There were significant alterations in the pattern of total ventricular MBG distribution in favor of the RV. Because RV myocardium received proportionate increments to its endocardium as well as epicardium, it is concluded that autoregulation in the RV coronary vascular bed had not been abolished even during hypoxia + RVSH. Marked increase in MBF to the right side of the septum during each RVSH with little change in perfusion to other regions suggests that RV contraction is supported by the right side of the septum. Because these increments occurred with decreased RV coronary driving pressure they were the consequence of compensatory coronary vasodilatation. The slow heart rate of the pony in the presence of a large coronary vasodilatory reserve may have been the major factor in allowing large increments in MBF to the stressed regions despite decreased coronary driving pressure.
Ventilation, metabolism, arterial blood gases, and blood and cerebrospinal fluid (CSF) acid-base status were measured in exercise studies on seven ponies during mild, moderate, and near-maximal treadmill exercise. CSF and arterial blood were sampled via indwelling catheters. Generally measurements were made during the 3rd, 6th, and 9th minute of steady-state exercise, with CSF sampled only during the 9th minute. Alveolar ventilation (VA) and metabolic rate (VO2) increased proportionately during exercise below the anaerobic threshold, but above this threshold, VA increased at a faster rate than VO2. The similarity of these response to those observed in man suggests the pony is a suitable animal model for study of exercise hyperpnea. No change in CSF acid-base balance occurred with light-to-moderate work; however, with near-maximal work a fall in CSF carbon dioxide partial pressure due to hyperventilation caused CSF to become alkaline (pH = 7.380) relative to rest (pH = 7.330). CSF lactate increased slightly with exercise but had no effect on CSF [HCO3-], which remained constant from rest to severe exercise. We conclude that it is unlikely the hyperpnea at any intensity of exercise results from an increased H+ stimulation at the medullary chemoreceptor.
Administration of glucagon has been shown to decrease pulmonary vascular resistance, but its primary site of action is undetermined. Whether this is on the arterial or venous side of the capillary would be reflected in the microvascular hydrostatic pressure. We used the pulmonary flow of lymph, a sensitive index of the transvascular fluid filtration rate, to monitor the microvascular hydrostatic pressure. Eight unanesthetized sheep with a surgically created long-term fistula for monitoring pulmonary lymph were given a 3-mg bolus of glucagon after a baseline period. We found no change in pulmonary arterial or left atrial pressures but noted a significant increase in cardiac output and a decrease in pulmonary resistance. The flow of pulmonary lymph increased by 50 percent for 30 minutes after administration of glucagon, and the protein content of the lymph decreased by 15 percent, indicating a large increase in the microvascular hydrostatic pressure. From these data, we calculated a decrease in arterial resistance from 60 percent to 30 percent of the total and, subsequently, an increase of 6 cm H2O in the microvascular hydrostatic pressure. Administration of glucagon, therefore, decreases the arterial resistance while increasing microvascular pressure in the process.
Repeated pulmonary function testing was performed on six 4- to 6-week-old resting, nonanesthetized Holstein-Friesian calves (av weight 59 kg). Under study conditions, PaO2, PaCO2 and pH were 73.3 mm of Hg, 41.2 mm of Hg, and 7.42, respectively. Mean ventilatory values for the group were: minute ventilation, 13.1 L/min/m2., and respiratory rate, 27.3 breaths/minute. Measurements of pulmonary mechanics were performed while animals breathed spontaneously through a pneumotachygraph. Intrapleural pressure was estimated, using an esophageal balloon-catheter. Total pulmonary resistance was 3.1 cm of H2O/L/sec and dynamic pulmonary compliance was 0.15 L/cm of H2O. These values have not been reported previously in the calf but agreed well with predicted values derived from comparative studies in other species. Efficiency of intrapulmonary gas mixing was estimated, using a N2 washout technique, and results agreed favorably with values previously reported in the dog.
Pulmonary function changes in 6 Holstein-Friesian calves, 4 to 8 weeks of age, were studied for 10 to 11 days following experimental inoculation with infectious bovine rhinotracheitis (IBR) virus. Calves had no demonstrable antibody titer against IBR virus before inoculation, and all calves responded to the virus by postinoculation day 3 with high fever (greater than 40.6 C) and rapid, shallow breathing. Analysis of blood gases demonstrated a progressive rise in PaCO2 but no change in PaO2. Acid-base state remained normal. Tidal volume decreased with time; conversely, minute ventilation functional residual capacity, O2 consumption, and CO2 production increased. Alveolar ventilation failed to increase as much as predicted. Studies of respiratory mechanics showed a progressive increased in total pulmonary resistance but without change in dynamic pulmonary compliance. A steady-state N2 washout test was used with these calves, and results suggested impairment of intrapulmonary gas mixing as the disease progressed. Microbiologic, pathologic, and histopathologic analyses were consistent with the picture of acute IBR. This study demonstrated our ability to measure pulmonary function changes in nonanesthetized large animals suffering from respiratory tract disease. We characterized the pathophysiologic features of acute IBR infection in the bovine species as an obstructive lung disease resulting in increased resistance to breathing, retention of CO2, and increased resting lung volume.
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