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Biomedical subjects

B H Hoff

Publications and source records attributed to B H Hoff.

At least 19 recordsLinked to original sources

Resolution of derivatives of 1,2-propanediol with lipase B from Candida antarctica. Effect of substrate structure, medium, water activity and acyl donor on enantiomeric ratio.

The glycerol-related racemic derivatives 1a-15a and 1b-15b have been resolved by hydrolysis and transesterifications using lipase B from Candida antarctica. Influence of substrate structure for the enantiomeric ratio E has been explained on the basis of previous molecular modelling. E values and equilibrium constants Keq have been calculated on the basis of ees and eep measured throughout the reaction, and ping-pong bi-bi mechanism using the computer program E&K calculator. Medium effects have been studied for hydrolysis with organic co-solvents and transesterifications in different solvents with varying water activity, aw. For some substrates addition of 30% acetone to the hydrolysis reaction gave a large increase of E. High water activity gave for some substrates an increase of E, but was unfavourable for the reversibility. However, this did not significantly influence the ee of product fraction. The influence of the alkoxy part of various butanates as acyl donors has been studied with respect to E and Keq. It was generally found that 2-chloroethyl butanate gave higher E than vinyl butanate; however, the latter gave irreversible conditions.

Acylation

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals

Effects of PEEP on acinar gas transfer in healthy and lung-injured dogs.

We measured cardiorespiratory variables and 133xenon washout from a nonperfused lung region (XeW) in six anesthetized/paralyzed dogs, mechanically ventilated with 60% O2 at different positive end-expiratory pressures (PEEP). XeW in this technique represents directly measured acinar gas transfer (3). Measurements were repeated after induction of lung injury by lavaging the lungs 11 to 13 times with 600 ml saline. In control dogs, lung compliance (CL), alveolar ventilation (Valv), and XeW all decreased with increasing PEEP from 0 to 25 cm H2O (p < 0.05), while lung resistance (RL) did not change. After lavage, CL, Valv, and XeW below 15 cm H2O PEEP were all less than control values (p < 0.05), while RL was higher than control values. As PEEP increased from 0 to 20 cm H2O, Valv and XeW increased, but CL did not change; RL decreased only from 0 to 5 cm H2O. At 20 cm H2O PEEP, Valv and CL were not different from control values (p > 0.05), and XeW was higher than control values (p < 0.05). At estimated alveolar volumes above 400 ml, values for XeW before and after lavage were similar. We conclude that, during severe lung injury: (1) increasing PEEP to moderate levels will increase acinar gas transfer but, after a certain lung volume is reached, further increases in PEEP will have effects similar to the healthy condition; (2) overall mechanical properties of the lung do not reflect the responses to PEEP of the lung periphery.

Animals

Transfer of gas from the acinus during continuous flow and intermittent positive pressure ventilation.

We used a technique of measuring Xenon133 washout (XeW) from the alveolar space to evaluate transfer of gas from the acinus (Mackenzie et al., J. Appl. Physiol. 68: 2013-2018, 1990) during 2 min of apnea, 2 min of tracheal insufflation with oxygen (TRIO) and 90 sec of intermittent positive pressure ventilation (IPPV) in 6 anesthetized and paralyzed dogs. Xenon133 dissolved in saline was injected into an occluded acinar region through a pulmonary artery catheter, and XeW was measured by gamma scintillation scanning. With this technique, XeW during apnea represents the contribution of cardiogenic oscillations in regional flow. The XeW rate constant (min-1 +/- SE) was 0.37 +/- 0.03 during apnea. This was not different (P > 0.05) with TRIO (0.29 +/- 0.04). With IPPV, the rate constant increased to 3.49 +/- 0.39, faster than with either apnea or TRIO (P < 0.001). We conclude that: (1) TRIO does not increase convective gas transfer from the acini compared to apnea; and (2) transfer of gas out of the acini due to cardiogenic oscillations is a very small portion of the total gas eliminated during IPPV.

Animals

Effect of pulmonary edema on transfer of gas from acinus to airways.

We directly measured the effect of progressive pulmonary edema on gas transfer from the acinus by injecting 133Xe dissolved in saline through a pulmonary artery catheter into an acinar region with occluded blood flow and measuring 133Xe washout by gamma scintillation scanning. We measured washout in six anesthetized paralyzed dogs during mechanical ventilation with O2 before and after injection of 0.6 mg/kg of oleic acid into the right atrium, which induces severe pulmonary edema within 2 h. Changes in the elastance and resistance of the lung were also calculated from measurements of airway flow, airway pressure, and esophageal pressure. Before injection of oleic acid, the monoexponential rate constant for 133Xe washout was 3.6 +/- 1.4 (SE) min-1; from this we estimated that the rate of gas transfer of 133Xe from the acini was 1.0 l/min. The rate constant decreased gradually after the injection and was correlated with increases in elastance and resistance (r = -0.66) and decreases in alveolar PO2 (r = 0.71). At 2 h after injection, the rate constant (1.2 +/- 0.8 min-1) was lower than control (P < 0.01), and the rate of gas transfer of 133Xe from the acini was < 0.32 l/min. We conclude that resistance in the acini is increased during pulmonary edema and that it is correlated, in the oleic acid model, with changes in overall lung mechanical properties.

Animals

Collateral ventilation of obstructed lung during high-frequency oscillation in dogs and pigs.

To determine if collateral ventilation (CV) occurs in pigs and dogs during intermittent positive-pressure ventilation (IPPV) and high-frequency oscillation (HFO), seven pigs and seven dogs were studied by measuring Xenon 133 washout (XeW) from an occluded subsegmental bronchus. The rate constant/min (K) for Xe blood uptake (KXeb) was derived, and when subtracted from K for XeW (KXeW) gave K for removal of Xe by CV (KXecv). Pig XeW were single exponentials with mean KXew = 0.25/min during IPPV and 0.12/min with HFO. In pigs, mean K of XeW was no different from KXeb so that all XeW occurred by blood uptake and none by CV. XeW in dogs had two exponentials. Dogs had over 11 times greater mean KXeW than pigs during IPPV and over 24 times greater during HFO. In dogs, on average, 79% (IPPV) and 87% (HFO) of XeW occurred by CV. CV is a means of gas exchange during HFO and IPPV in dogs but not in pigs.

Animals

Acute digitalis toxicity during TURP.

Water entrainment into opened prostate venous sinuses during transurethral resection of the prostate (TURP) may lead to dilution of serum electrolytes. Dilutional hypokalemia may precipitate digitalis toxicity in the digitalized patient. Successful resuscitation of such a patient is reported.

Arrhythmias, Cardiac

Conventional and high-frequency ventilation in dogs with bronchopleural fistula.

Seven anesthetized dogs with bronchopleural fistulas were subjected to a sequence of continuous positive-pressure ventilation (CPPV), volume-controlled high-frequency positive-pressure ventilation (HFPPV), and high-frequency vibratory ventilation (HFVV). Adequate short-term ventilation and oxygenation were possible with all three ventilatory modes. During HFPPV and HFVV, PaCO2 was unchanged, but hypercarbia developed during CPPV. PaO2 decreased during each mode of ventilation, but HFPPV maintained PaO2 at a sufficient and constant level during the 30-min test period. HFPPV was the most efficient technique with respect to delivery of minute ventilation, the relation between fistula flow and delivered ventilation, and maintenance of both ventilation and oxygenation.

Animals

Percutaneous transtracheal jet ventilation for cardiopulmonary resuscitation: evaluation of a new jet ventilator.

This study compared percutaneous transtracheal jet ventilation (PTJV) at a frequency (f) of 20/min, with high-frequency positive-pressure ventilation (HFPPV) at f of 60/min, and endotracheal intubation and intermittent positive-pressure ventilation (ET IPPV) at f of 10/min in apneic dogs. Fifty-four emergency medicine trainees (EMTs) attempted PTJV via a 14-gauge Angiocath attached to a hand-held jet ventilator, f of 20/min, and ET IPPV using an Ambu bag, f of 10/min. Twenty-nine other EMTs attempted cricothyrotomy using a prototype nonkinkable catheter (Arrow) and a new jet ventilator, Bronchovent, f of 60/min, equipped with a pressure sensor which stops ventilation at pressures greater than 20 cm H2O. Adequate oxygenation was achieved by all 3 groups, but only the HFPPV group avoided respiratory alkalosis. There was a higher equipment failure rate (catheter kinking and dislodgment) in the PTJV group. In the HFPPV group, the Bronchovent's pressure-limiting sensor stopped ventilation when the catheter was kinked or out of position, reducing the extent of subcutaneous emphysema and barotrauma. With further catheter improvements, HFPPV Bronchovent may offer a safe and reliable method of ventilating patients during CPR in the field.

Alkalosis, Respiratory

Perioperative management in undiagnosed pheochromocytoma.

Pheochromocytoma which is diagnosed intraoperatively carries a high morbidity and mortality. Successful management of the patient with unsuspected pheochromocytoma requires a high index of suspicion and aggressive pharmacologic intervention.

Adrenal Gland Neoplasms

Intermittent positive pressure ventilation and high frequency ventilation in dogs with experimental bronchopleural fistulae.

This study evaluated respiratory and cardiovascular responses of canines in whom bilateral bronchopleural fistulae were created surgically, and in whom ventilation was varied between intermittent positive pressure ventilation (IPPV) and high frequency ventilation (HFV). An Emerson prototype ventilator was used for HFV at rates of 300-1400/min at driving pressures of 2.5, 5.0, and 10 psi. Gas exchange was judged by arterial and mixed venous blood gases. Cardiac performance was measured by cardiac index, heart rate, stroke index, stroke work index, systemic and pulmonary vascular pressures and resistances. Ventilation during IPPV with the fistula open resulted in a statistically significant increase in PaCO2 and a decrease in PaO2 when compared to both HFV modes. Variations in cardiac function in these open-chested animals were insignificant for all variables tested except pulmonary artery pressures which rose significantly in the IPPV group.

Animals

High frequency ventilation in dogs with open chests.

This study evaluated and compared the physiological responses to high frequency percutaneous transtracheal ventilation in dogs before and after median sternotomy thoracotomy. Standard intermittent positive pressure ventilation (IPPV) was established before and after high frequency rates (100 and 300 breath/min) with the chest closed and then after thoracotomy. Gas exchange as judged by arterial and mixed venous blood gases, and cardiac performance as judged by pulmonary capillary wedge pressure, pulmonary and systemic arterial pressures, vascular resistances, and cardiac index all remained clinically acceptable. Physiologically, ventilation in the open chest condition was adequate but was associated with a slight decrease in PaCO2 and a decrease in PaO2. Peak and mean airway pressures were similar for IPPV and high frequency modes of ventilation.

Animals

Long-term transtracheal high frequency ventilation in dogs.

Long-term effects of high frequency percutaneous transtracheal ventilation (HFTV) have not been studied. The purpose of this study is to evaluate the cardiopulmonary effects of 24 h transtracheal ventilation in dogs at a respiratory rate of 100/min. Four dogs were anesthetized with intermittent pentobarbital and paralyzed with pancuronium. Ventilation in the supine position was through a 14-gauge Angiocath introduced into the trachea through the cricothyroid membrane. A respiratory rate of 100/min was used at an FIO2 of 0.4 using a fluidic logic controlled ventilator. The inspiratory-expiratory ratio was 1:2 and tidal volume 70 ml. The driving pressure of the air-oxygen mixture was 50 psi. After 24 h, residual muscle relaxant was reversed and the animal allowed to recover. There was no significant change in the following parameters over 24 h compared to starting values: PaO2, PaCO2, pH, aortic, central venous, pulmonary artery and pulmonary artery wedge pressures, heart rate, cardiac index (CI), stroke index (SI), left ventricular stroke work (LVSW), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), C(a-V)O2, oxygen consumption (VO2), pulmonary shunt (Qs/Qt). A PEEP effect of 2.9 - 5.0 torr was maintained. All dogs recovered uneventfully. Three days after the experiment, blood gases of 2 dogs were normal. One dog was killed after 3 days; macroscopic and microscopic examinations of the upper and lower airway and pulmonary parenchyma were normal. Dogs can be ventilated for as long as 24 h using HFTV transtracheally at rates of 100/min without adverse cardiopulmonary effects.

Animals

Use of positive airway pressure without endotracheal intubation.

Continuous positive airway pressure (CPAP) and expiratory positive airway pressure (E-PAP) may be used safely without endotracheal intubation in patients with acute respiratory failure when strict selection criteria are adhered to. The therapy should be titrated to reduce intrapulmonary shunting, improve PaO2, and reduce FIO2. Other considerations include balancing oxygen consumption against cardiac output and oxygen transport. Absolute or relative indications for abandoning the technique and using endotracheal intubation with mechanical ventilatory support include unrelenting hypoxia, patient exhaustion, rising PaCO2, development of metabolic acidosis, presence of ventricular arrhythmias, and inability to protect the airway.

Acute Disease

Multisystem failure: a review with special reference to drowning.

Near-drowning represents an insult that can affect all organ systems. A common pathway for injury is hypoxemia, acidosis, and hypoperfusion. Pulmonary insufficiency and CNS dysfunction are major causes of morbidity and mortality. Variations in vascular volume, heart failure, renal failure, coagulation disorders, and electrolyte disturbances may also be present. Patients should be observed for multisystem failure and therapy tailored to the particular needs of each victim.

Acidosis