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Biomedical subjects

R B Weiskopf

Publications and source records attributed to R B Weiskopf.

At least 91 records · Page 5Linked to original sources

Determination of plasma volume in swine by the enzyme-dilution method.

Plasma volume of six young swine was determined by simultaneous dilution in the plasma of two purified porcine enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and Evans blue dye. Ninety-minute time-activity and time-concentration curves were obtained, and the dilution spaces of each plasma indicator at the time of injection were estimated by extrapolation of data from the first 30 min after injection. Plasma volumes estimated using the two enzymes agreed closely with each other (AST, mean 50.2 ml/kg; ALT, mean 49.8 ml/kg) and were 11% smaller than those determined using Evans blue dye (mean 56.3 ml/kg). Plasma volumes calculated from the AST and ALT activities and Evans blue dye concentration in a sample drawn 5 min after injection very closely approximated those obtained by extrapolation. These values were comparable to previously published estimates of plasma volume for swine of equivalent weight. Endogenous plasma levels of AST and ALT activity were measured in samples drawn from five swine before and after a 40% blood loss. No significant change in AST or ALT activities occurred after hemorrhage.

Alanine Transaminase↗

Effects of fentanyl on vasopressin secretion in human subjects.

To test the influence of an opioid on vasopressin (AVP) secretion, plasma AVP concentration was measured in five semirecumbent unmedicated volunteers before and during two continuous i.v. infusions of fentanyl. Infusion rates were adjusted to produce steady-state plasma fentanyl concentrations of 2.0 +/- 0.4 and 4.1 +/- 0.6 ng/ml; mild to moderate hypercarbia was induced during the control and infusion periods. Fentanyl increased plasma AVP concentration in a dose-dependent manner to 559 +/- 215 and 929 +/- 199% of the basal level of 1.9 +/- 0.7 pg/ml. Neither mild hypercarbia (PCO2 = 50 +/- 1 mm Hg) in the absence of fentanyl nor moderate hypercarbia (PCO2 = 66 +/- 3 mm Hg) in the presence of fentanyl changed plasma AVP concentration. Neither fentanyl nor hypercarbia, nor the combination of the two, altered plasma renin activity.

Adult↗

Haemorrhage decreases the anaesthetic requirement for ketamine and thiopentone in the pig.

The anaesthetic requirements of ketamine and thiopentone were studied in eight pig littermates during normovolaemia and after haemorrhage (30% blood loss). Four animals received ketamine and four thiopentone, and the minimal anaesthetic doses of both drugs were determined. Moderate hypovolaemia decreased the anaesthetic requirements significantly and similarly: thiopentone 33 +/- 5%; ketamine 40 +/- 5% (mean +/- SEM).

Anesthesia, Intravenous↗

Cardiovascular actions of nitrous oxide or halothane in hypovolemic swine.

During normovolemia, nitrous oxide causes mild sympathetic stimulation and direct myocardial depression; these effects offset each other, resulting in only minimal cardiovascular changes. To test the hypothesis that during hypovolemia this balance would change and depression predominate, 10 swine were made hypovolemic (30% blood loss) and then were given 70% N2O (0.25 MAC in swine) or an equipotent concentration of halothane, an agent that does not cause sympathetic stimulation. The alternate anesthetic was given to the same hypovolemic swine on another day. Five minutes after induction of anesthesia during hypovolemia, both N2O and halothane caused significant, physiologically important deterioration of compensation for hemorrhage. Halothane decreased systemic vascular resistance (SVR); N2O was more variable in its action, and SVR did not decrease significantly. Both agents caused similar decreases in cardiac output, mean aortic blood pressure, stroke volume, oxygen consumption, and left ventricular minute work, despite increases in plasma epinephrine concentration and plasma renin activity. No differences were found between groups for any of these variables (P greater than 0.05). Plasma norepinephrine concentration increased only in the N2O group and was greater in that group than in the halothane group. The deterioration of cardiovascular compensation for hemorrhage was expressed metabolically by similar decreases in the two groups in partial pressure of oxygen of mixed venous blood and by increases in blood lactate concentration. Thirty minutes after induction of anesthesia, with stable end-tidal anesthetic concentrations, both groups had some cardiovascular, but no metabolic, recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Cardiovascular and metabolic sequelae of inducing anesthesia with ketamine or thiopental in hypovolemic swine.

If further sympathetic stimulation is neither possible nor desirable during moderate hypovolemia, anesthetic agents capable of sympathetic stimulation would not be advantageous for induction of anesthesia during hypovolemia. To test this hypothesis, 21 swine were studied during normovolemia and after 30% of their estimated blood volume was removed. Swine were divided randomly into three equal groups to receive no anesthetic or the minimal anesthetic dose of ketamine (6.65 +/- 0.38 mg/kg, iv) or thiopental (5.77 +/- 0.21 mg/kg, iv). After the initial response to hypovolemia, animals given no drug did not exhibit further changes during the hypovolemic period. Five minutes after induction of anesthesia in the hypovolemic state, ketamine, but not thiopental, caused large increases in plasma epinephrine, norepinephrine, and renin activity. Despite these differences, both anesthetics equally depressed systemic vascular resistance, mean systemic arterial blood pressure, heart rate, and cardiac output. Ketamine, but not thiopental, decreased stroke volume. Neither anesthetic affected oxygen consumption. Both anesthetics caused similar increases in blood lactate concentration. Thirty minutes after induction of anesthesia, plasma epinephrine, norepinephrine, and renin activity remained higher in animals given ketamine than in those given thiopental. Stroke volume, systemic vascular resistance, cardiac output, and oxygen consumption did not differ among groups; however, only the animals given ketamine showed further increase in blood lactate concentration and base-deficit. Thirty minutes after infusion of shed blood, cardiac output and blood lactate concentration were greater in the animals given ketamine than in those given thiopental or no anesthetic. Ninety minutes after infusion of shed blood, no differences existed among groups. The authors conclude that after moderate hemorrhage, further increase in circulating catecholamines is possible but that the levels achieved either exceed the maximal effective concentration at site(s) of action or their effects are overwhelmed by the depressant effects of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Minimum alveolar concentrations (MAC) of halothane and nitrous oxide in swine.

To compare anesthetic effects using a swine model, we needed to know the minimum alveolar concentrations (MAC) of halothane and nitrous oxide that produce anesthesia in the pig. This information does not exist in literature. Furthermore, MAC varies considerably among species: by more than 60% for halothane, and by more than 200% for nitrous oxide. Therefore, using eight young swine, we determined mean (+/- SEM) MAC values for halothane (1.25 +/- 0.04% of one atmosphere) and nitrous oxide (277 +/- 18% of one atmosphere). These values are higher than values reported for other mammals. Factors possibly accounting for this variability include interspecies differences, age, body temperature, increased sympathetic activity, and differences in methodology.

Animals↗

Acid-base curve and alignment nomograms for swine blood.

To construct acid-base curves and alignment nomograms for swine blood, we added known amounts of acid or base to aliquots of swine blood with three different concentrations of hemoglobin. Pairs of blood samples were equilibrated at two different CO2 partial pressures, and blood pH was measured. Data were analyzed by computer, and mean values were created for complete data of four swine. Curve and alignment nomograms were constructed by computer. The resultant nomograms for swine blood differ from those constructed by Siggaard-Andersen for human blood, most importantly at base-excess values of +10 to +25 mmol/l. The possible reasons for the observed differences are discussed and, although not completely resolved, may be related in large measure to the accuracy of pH determination and the methodology of nomogram construction.

Acid-Base Equilibrium↗

Oxygen-linked hydrogen ion binding of canine blood.

Decrease in hemoglobin oxygen saturation without change of true blood base-excess results in an increase in calculated base-excess because of differences in acidity between oxy- and deoxyhemoglobin. We have determined the mean +/- SE canine base-excess correction coefficient to be 0.43 +/- 0.01 mmol base per mmol heme, a value approximately 34% higher than the corresponding value for human hemoglobin.

Animals↗

Effects of halothane and morphine sulfate on myocardial compliance following total cardiopulmonary bypass.

We evaluated the effect on diastolic myocardial compliance of halothane and morphine sulfate using 15 swine placed on total cardiopulmonary and right heart bypass with controlled aortic pressure, heart rate, and left ventricular preload. The animals were divided into three equal groups: (I) regional block anesthesia, (II) morphine sulfate (10 mg/kg), and (III) halothane anesthesia at 0.5%. Myocardial performance was evaluated on right heart bypass following a 30 minute period of total cardiopulmonary bypass before and after administration of the anesthetic agent by measuring stroke volume, left ventricular end-diastolic pressure, and left ventricular end-diastolic volume. All perfusions were at normothermia, at a hematocrit level of 30%, and at a normal arterial Po2. PCO2, and pH. Neither regional block nor morphine sulfate anesthesia significantly depressed the myocardium or changed diastolic compliance. Halothane, however, significantly decreased diastolic compliance so that stroke volume was less at a given left ventricular end-diastolic pressure, but not at a given left ventricular end-diastolic volume. The depression of stroke volume with halothane following cardiopulmonary bypass at equal filling pressures appears to be due primarily to a change in compliance rather than to a change in contractility.

Anesthesia↗

Extending the limits of hemodilution on cardiopulmonary bypass using stroma-free hemoglobin solution.

Ten swine were subjected to exchange transfusion to a hematocrit level of 5% with either stroma-free hemoglobin solution (SFHS) or 7% albumin solution. Myocardial performance, oxygen kinetics, and myocardial metabolism were subsequently examined using a perfused, in situ, right heart bypass, swine heart model with control of preload, afterload, and heart rate. Animals were tested during a control period (hematocrit = 30%) and following exchange transfusion with either solution to a hematocrit level of 5%. We found that myocardial performance following albumin solution exchange could not be sustained on right heart bypass, and these animals had a stroke volume of zero at a left ventricular end-diastolic pressure of 14 torr. SFHS animals had a significant drop in stroke volume at 14 torr following exchange (20 +/- 3 versus 10 +/- 4, p < 0.025), but this 50% performance level could be sustained. Coronary blood flow rose and myocardial oxygen consumption fell in both groups, although the statistically nonsignificant mean differences were less with SFHS. Arterial-coronary sinus oxygen difference fell significantly (p < 0.05) with albumin solution (7.3 +/- 0.8 versus 2.2 +/- 0.2) and nonsignificantly with SFHS (5.6 +/- 0.4 versus 4.1 +/- 0.7). Lactate production occurred in both groups, but was greater with albumin (34% +/- 6%) than with SFHS (3% +/- 16%). No changes in myocardial tissue gasses were noted in either group. Although myocardial performance decreased and some lactate production occurred with SFHS, we believe these comparative results provide promise in the eventual utilization of an oxygen-carrying agent such as SFHS to extend the limits of hemodilution to a hematocrit value of 5% or less.

Animals↗

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.

In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.

Acid-Base Equilibrium↗

Amelioration of the symptoms of acute mountain sickness by staging and acetazolamide.

Treatment by 4 d of residence at 1600 m plus the administration of 500 mg acetazolamide b.i.d. for the last 2 d at 1600 m and the first 2 d at 4300 m was compared with no treatment prior to ascent to 4300 m for prophylaxis of acute mountain sickness. The treatment successfully prevented almost all symptoms of acute mountain sickness. It had no effect on the diminished capacity for maximal or prolonged heavy physical work. The treatment produced a relative acidosis and a comparatively greater arterial oxygen tension at 4300 m.

Acclimatization↗

Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man.

By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude.

Adult↗