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Biomedical subjects

D M Philbin

Publications and source records attributed to D M Philbin.

At least 19 recordsLinked to original sources
PubMed1995

Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery.

Although eicosanoid production contributes to physiological and pathophysiological consequences of cardiopulmonary bypass (CPB), the mechanisms accounting for the enhanced eicosanoid production have not been defined. Plasma phospholipase A2 (PLA2) activity, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) levels were measured at various times during cardiac surgery. Plasma PLA2 activity increased after systemic heparinization, before CPB. This was highly correlated with concurrent increases in plasma 6-keto-PGF1 alpha, TXB2 concentrations did not increase with heparin administration but did increase significantly after initiation of CPB. High plasma PLA2 activity, 6-keto-PGF1 alpha, and TXB2 concentrations were measured throughout the CPB period. Protamine, administered to neutralize the heparin, caused an acute reduction of both plasma PLA2 activity and plasma 6-keto-PGF1 alpha, but no change in plasma TXB2 concentrations. Thus the ratio of TXB2 to 6-keto-PGF1 alpha increased significantly after protamine administration. Enhanced plasma PLA2 activity was also measured in patients with lower doses of heparin used clinically for nonsurgical applications. Human plasma PLA2 was identified as group II PLA2 by its sensitivity to deoxycholate and dithiothreitol, its substrate specificity, and its elution characteristics on heparin affinity chromatography. Heparin addition to PMNs in vitro resulted in dose-dependent increases in cellular PLA2 activity and release of PLA2. The PLA2 released from the PMN had characteristics similar to those of post-heparin plasma PLA2. In conclusion, plasma PLA2 activity and 6-keto-PGF1 alpha concentrations are markedly enhanced with systemic heparinization. Part of the anticoagulant and vasodilating effects of heparin may be due to increased plasma prostacyclin (PGI2) levels. In addition the pulmonary vasoconstriction sometimes associated with protamine infusion during cardiac surgery might be due to decreased plasma PLA2 activity, with an associated increased TXB2/6-keto-PGF1 alpha ratio.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Post-ischemic diastolic dysfunction.

Though a sustained post-ischemic decrease in contractile function has been clearly established, post-ischemic diastolic function has not been thoroughly investigated. Accordingly, 11 anesthetized (isoflurane 1%) open-chest beagles were instrumented to measure left ventricular pressure and dimensions (circumferential length and wall thickness) in an apicoanterior area supplied by the left anterior descending coronary artery (LAD). Pressure-dimension relations were modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 minutes partial occlusion of the LAD (systolic bulging), and 60 minutes after the onset of reperfusion. Stiffness constants were derived from the end-diastolic pressure-length and stress-strain relations, respectively. Myocardial ischemia was associated with significant (P < 0.05) alterations of the following parameters of diastolic function: (1) 47% increase in end-diastolic pressure; (2) 22% decrease in peak negative dP/dt; (3) 9% increase in the time constant of isovolumic relaxation (tau); (4) postcystolic contraction; (5) 6% increase in end-diastolic length and 10% decrease in end-diastolic thickness; (6) 12% increase in unstressed length (creep) and 13% decrease in unstressed thickness; (7) 51% increase in chamber stiffness and a 63% increase in myocardial stiffness; and (8) 40% decrease in the peak lengthening rate. After 60 minutes of reperfusion, only end-diastolic pressure and tau had returned to baseline values whereas systolic shortening fraction, postsystolic contraction, and end-diastolic and unstressed dimensions had only partially recovered. No recovery occurred in peak negative dP/dt, chamber stiffness, myocardial stiffness, and peak lengthening rate. Thus, both myocardial ischemia and reperfusion are associated with complex changes in global and regional left ventricular diastolic function.

Anesthesia, Inhalation↗
PubMed1993

Epileptiform activity during opioid anesthesia.

The proconvulsant properties of exogenously administered opioids in man are not established. We prospectively evaluated relationships between epileptiform activity and opioid dose in 20 patients undergoing coronary artery revascularization. Baseline electroencephalograms were performed before surgery. Ten subjects were given fentanyl and 10 sufentanil, at 100 micrograms/kg and 10 micrograms/kg, respectively, in 4 divided doses, 3 min apart. Midazolam (4 mg) was given 3 min after the last dose of narcotic. Serum opioid concentrations were measured by radioimmunoassay. Within 3 min of the first opioid dose, 19 of 20 patients developed epileptiform activity, characterized by generalized single and multiphasic, low-to-moderate voltage spike discharges, similar in appearance to benign epileptiform transients of sleep (BETS). Despite continuously increasing serum concentrations of opioid, the number of spike discharges initially increased during the first and second dose intervals and then declined during the third and fourth dose intervals. This dissociation between epileptiform discharges and measured serum opioid concentration was unexpected and remained unexplained. Spike activity was consistently attenuated (P = 0.000003) within 20 sec of midazolam administration. Abrupt cessation of discharges after administration of the anticonvulsant, midazolam, suggests an epileptogenic mechanism for the opioid-induced activity.

Anesthesia, General↗
PubMed1992

Indications for the use of pacing pulmonary artery catheters in cardiac surgery.

Several varieties of pulmonary artery catheters (PACs) with pacing capabilities are now available. Although specific recommendations for prophylactic perioperative placement of pacemakers have been offered previously, the authors believe that those recommendations warrant further examination, taking into consideration the availability of new pacing modalities. Toward this end, the use of pacing PACs in cardiac surgical patients was prospectively examined. In 600 consecutive adult patients with PACs placed prior to cardiopulmonary bypass (CPB), the cardiac anesthesiologist recorded if a pacing PAC was placed, the indications for placing it, and whether the catheter was used to pace. If a pacing PAC was not chosen, the anesthesiologist indicated whether cardiac pacing was needed prior to CPB. In all patients, the presence and specifics of the following five possible indications were documented: sinus node dysfunction/bradydysrhythmias, atrioventricular heart block, fascicular or bundle branch block, cardiac reoperation, and/or valvular heart disease. PACs with pacing capability were placed in 180 of the 600 patients (30.0%) and were used in 34 of these 180 patients (18.8%). In 4 of 420 patients (0.95%) without pacing PACs, cardiac pacing was needed prior to CPB. The following preoperative diagnoses were significant predictors (P less than .05) for the use or need for pacing catheters: sinus node dysfunction/bradydysrhythmias, a history of transient complete atrioventricular block, aortic stenosis, aortic insufficiency, and reoperation. The majority of adult patients undergoing cardiac surgery do not require the use of a pacing PAC prior to CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass.

Normothermic cardiopulmonary bypass (CPB) is used in cardiac surgery at some institutions. To compare hemodynamic and hormonal responses to hypothermic (29 degrees C) and normothermic nonpulsatile CPB, 20 adults undergoing coronary artery bypass graft and/or aortic valve replacement were studied. Hemodynamic measurements and plasma hormone concentrations were obtained from preinduction to the third postoperative hour. The two groups were given similar amounts of anesthetics and vasodilators. Systemic vascular resistance increased only during hypothermic CPB, and heart rate was higher at the end of hypothermic CPB. Postoperative central venous pressure and pulmonary capillary wedge pressure were lower after hypothermic CPB. Oxygen consumption decreased by 45% during hypothermic CPB, did not change during normothermic CPB, but increased similarly in the two groups after surgery; mixed venous oxygen saturation (SvO2) was significantly lower during normothermic CPB. Urine output and composition were similar in the two groups. In both groups, plasma epinephrine, norepinephrine, renin activity, and arginine vasopressin concentrations increased during and after CPB. However, epinephrine, norepinephrine, and dopamine were 200%, 202%, and 165% higher during normothermic CPB than during hypothermic CPB, respectively. Dopamine and prolactin increased significantly during normothermic but not hypothermic CPB. Atrial natriuretic peptide increased at the end of CPB and total thyroxine decreased during and after CPB, with no difference between groups. This study suggests that higher systemic vascular resistance during hypothermic CPB is not caused by hormonal changes, but might be caused by other factors such as greater blood viscosity. A higher perfusion index during normothermic CPB might have allowed higher SvO2.

Aortic Valve↗
PubMed1992

Anoxia-induced extracellular ionic changes in CNS white matter: the role of glial cells.

The rapid changes in brain extracellular ion concentrations that occur with anoxia are important in understanding the pathophysiology of anoxic-ischemic brain injury. While previous studies have focused on the ionic changes that occur in gray matter areas of the brain, white matter (WM) is also damaged by anoxia. We describe the changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) that accompany anoxia in WM, and present new results indicating that glial cells directly contribute to the observed fluctuations of these ions. Anoxia-induced changes in [K+]o and pHo were measured with ion-selective microelectrodes in the isolated rat optic nerve, a typical WM tract. To assess the contribution of glial cells, recordings were also made in optic nerves that contained only glial cells (produced by neonatal enucleation). Anoxia in WM produced less extreme changes in [K+]o and pHo than are known to occur in gray matter; in WM during anoxia, the average maximum [K+]o was 14 +/- 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 +/- 0.07 pH unit. These extracellular ionic changes were accompanied by rapid shrinkage of extracellular space volume. The ability of optic nerve axons to conduct action potentials was lost in temporal association with the increase in [K+]o. Increasing bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 +/- 0.08 pH unit) and a smaller average increase in [K+]o (9.2 +/- 2.6 mM). The increased glucose concentration presumably enhanced anaerobic metabolism, leading to extracellular lactate accumulation and a greater acid shift.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Con: colloids should not be added to the pump prime.

It is concluded that there is good scientific basis for an approach that avoids colloid priming solutions as routine for all adult CPB patients. There may be selected individuals who might benefit from colloid therapy; for instance, patients who are predicted to require high left atrial pressures postbypass, those who are borderline for getting through their surgical experience without a homologous red cell transfusion, and patients coming for surgery with a clinically important lung water elevation. In this time of cost constraints there are many more scientifically worthy therapies that could be made available to patients. We should focus on these and resist "luxury items" like routine colloid CPB priming solutions.

Cardiopulmonary Bypass↗
PubMed1990

Fentanyl and sufentanil anesthesia revisited: how much is enough?

This study was undertaken to determine if fentanyl and sufentanil could produce dose-related suppression of hemodynamic and hormonal responses to surgical stimulation. Eighty patients scheduled for elective CABG were studied in two consecutive protocols: protocol I was a randomized double-blind study of 40 patients who received a single dose of fentanyl (50 or 100 micrograms/kg) or sufentanil (10, 20, or 30 micrograms/kg). Hemodynamic measurements and hormonal concentrations (renin, aldosterone, cortisol, and catecholamines) were determined before and after induction and after intubation and sternotomy. Protocol II was an open randomized study of 40 patients who received sufentanil in one of four doses: 30 micrograms/kg as a single dose, 10 micrograms/kg plus infusion 0.05 microgram.kg-1.min-1, 20 micrograms/kg plus infusion 0.1 microgram.kg-1.min-1, or 40 micrograms/kg plus infusion 0.2 microgram.kg-1.min-1. Hemodynamic measurements and plasma sufentanil and catecholamine concentrations were determined before and after induction and after intubation, sternotomy, and aortic cannulation. Both protocols defined a hemodynamic response as a 15% or more increase in systolic blood pressure (SBP) from control and a hormonal response 50% or more increase over control. During protocol I, 18 patients had a hemodynamic response (average increase in SBP 22.6 +/- 2%) and 35 patients had a total of 59 hormonal responses. During protocol II, 24 patients had a hemodynamic response (average increase in SBP - 31 +/- 3%) and there were 15 catecholamine responses. There were no differences between dose groups in either protocol. It was concluded that in these dose ranges, suppression of hemodynamic or hormonal stress responses is not related to opioid dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1989

Variations in hemodynamic and stress hormonal responses in open heart surgery with buprenorphine/diazepam anesthesia.

The use of buprenorphine-diazepam-N2O (60%)-O2 anesthesia in open heart surgery was investigated. The authors examined the hemodynamic changes produced and the response of stress hormones. Twenty adult patients with atrial septal defects undergoing surgical correction were studied in two groups of 10, receiving either 6 micrograms/kg of buprenorphine (B6) or 12 micrograms/kg of buprenorphine (B12) for the induction of anesthesia. Both groups received a subsequent dose of 6 micrograms/kg of buprenorphine with the commencement of extracorporeal circulation (ECC). With surgery, mean arterial pressure showed a transient increase in both groups and thereafter was stable. Heart rate in the B6 group was increased from the onset of surgery to the day after, while the B12 group showed no significant change. Filling pressures showed no change in either group. Plasma catecholamine concentrations in the B6 group, in contrast to the B12 group, increased significantly from midoperation to after completion of the operation (ECC 10 minutes, B6 group v B12 group: plasma norepinephrine 616 +/- 231 v 195 +/- 38 pg/mL, plasma epinephrine 1385 +/- 392 v 572 +/- 132 pg/mL, P less than 0.05). Plasma ADH levels in both groups rose with the commencement of surgery, reaching a peak at ECC 10 minutes (B6 group 88.1 +/- 8.4 v B12 group 124.4 +/- 27.2 pg/mL). However, in contrast to plasma catecholamines, the antidiuretic hormone (ADH) levels in the B12 group remained higher until the first postoperative day. Therefore, patients who received the larger dose of buprenorphine had better control of hemodynamics and catecholamines, but a greater elevation of plasma ADH levels.

Adult↗
PubMed1989

Effect of verapamil on canine left ventricular function in the presence of fentanyl when apical blood flow is critically limited.

Instruments were inserted to seven dogs under halothane anaesthesia, to measure global and regional left ventricular function. Anaesthesia was continued with fentanyl (100 micrograms kg-1 bolus, then 1.5 micrograms kg-1 min-1). Critical constriction was applied to the left anterior descending coronary artery. Control recordings were made, followed by bolus administration of verapamil 0.08, 0.16 and 0.32 mg kg-1, with recordings 10 min after each bolus. At the highest dose, verapamil decreased systemic arterial pressure, left ventricular dP/dt, stroke volume and systemic vascular resistance, and increased heart rate significantly. Coronary perfusion pressure decreased and, in the presence of critical constriction, coronary flow per beat decreased significantly. In the region with constriction, systolic shortening of myocardium decreased and post-systolic shortening increased significantly with addition of verapamil. The addition of a high dose of verapamil to fentanyl anaesthesia caused reduction in systolic function and development of early diastolic dysfunction in myocardium with critically limited blood supply.

Anesthesia, Intravenous↗
PubMed1988

Effect of hypothermic hemodilutional cardiopulmonary bypass on plasma sufentanil and catecholamine concentrations in humans.

The effect of hypothermic hemodilutional cardiopulmonary bypass (CPB) on plasma sufentanil and catecholamine concentrations was studied in four groups of ten patients each, receiving four different doses of sufentanil. Samples for measurement of sufentanil were obtained before CPB, at 15, 30, and 45 minutes of CPB, during rewarming, immediately after and 15, 60, and 240 minutes after CPB. In addition, in groups III and IV, which received the highest dose of sufentanil, blood samples were also obtained for measurement of plasma levels of epinephrine and norepinephrine. Sufentanil concentration decreased in all groups with the start of CPB (group I, 2.92 +/- 0.2 to 2.04 +/- 0.2; group II, 3.30 +/- 0.3 to 1.51 +/- 0.2; group III, 7.08 +/- 0.7 to 3.45 +/- 0.3; group IV, 10.33 +/- 0.5 to 4.59 +/- 0.5 ng/ml). No further decreases occurred during CPB but increases occurred with rewarming. The first measurement after CPB approached the concentration before CPB (group I, 2.82 +/- 0.3; group II, 2.56 +/- 0.5; group III, 4.42 +/- 0.4; group IV, 6.10 +/- 0.4 ng/ml). Norepinephrine concentrations demonstrated a wide variability with no significant changes. Epinephrine levels increased significantly during rewarming in both groups (group III, 141 +/- 23 to 279 +/- 79 pg/ml; P less than 0.05; group IV, 105 +/- 24 to 267 +/- 68 pg/ml, P less than 0.05). The stability of plasma sufentanil concentrations during CPB suggest that no measurable metabolism or excretion occurred. The increase with rewarming and after CPB suggest significant sequestration.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1988

Intravenous diltiazem worsens regional function in compromised myocardium.

The effect of intravenous diltiazem on regional myocardial function was assessed in a canine model of critical constriction of the left anterior descending coronary artery (LAD). Maintenance anesthesia with fentanyl (1.5 micrograms.kg-1.min-1), 60% inspired nitrous oxide, and 0.7% inspired halothane resulted in regional dysfunction, measured as postsystolic shortening (20.6 +/- 10.7%), which was significantly worsened after 0.1 mg/kg (48.7 +/- 12.5%, P less than 0.05) and after 0.2 mg/kg (68.8 +/- 11.7%, P less than 0.05) intravenous diltiazem. Systolic shortening in the compromised LAD territory was substantially depressed after 0.1 mg/kg diltiazem (8.2 +/- 0.6% to 5.3 +/- 1.3%, P less than 0.05) and was essentially abolished after 0.2 mg/kg diltiazem (8.2 +/- 0.6% to 0.7 +/- 2.3%, P less than 0.05). At the higher dose of diltiazem, cardiac output was substantially decreased (1.37 +/- 0.23 L/min to 0.88 +/- 0.30 L/min, P less than 0.05) and LV dP/dtmax significantly depressed (1090 +/- 90 mm Hg/sec to 744 +/- 80 mm Hg/sec, P less than 0.05). These results demonstrate significant depression of regional systolic shortening and substantial worsening of regional dysfunction in myocardium with a compromised blood supply, in association with significant depression of left ventricular performance, with intravenous diltiazem administration during anesthesia.

Anesthesia, Inhalation↗
PubMed1988

Gradual or abrupt nitrous oxide administration in a canine model of critical coronary stenosis induces regional myocardial dysfunction that is worsened by halothane.

The existence of a dose-response relation between nitrous oxide concentration and regional dysfunction in compromised myocardium, and whether or not halothane-induced myocardial depression alleviated this regional dysfunction was examined. Nitrous oxide was administered to eight dogs with experimentally induced left anterior descending coronary artery (LAD) critical stenosis during fentanyl (100 micrograms/kg bolus plus 1.5 micrograms.kg-1.min-1) anesthesia. Two modes of nitrous oxide administration were employed: gradual (in steps of 20% inspired, i.e., 0%, 20%, 40%, and 60% inspired) and abrupt (0-60% inspired). Regional myocardial function was assessed by sonomicrometry. Regional dysfunction in the compromised myocardium, in the form of postsystolic shortening (PSS), increased above baseline levels during 40% (4.2 +/- 2.3% to 12.1 +/- 3.9%, P less than 0.05) and 60% (4.2 +/- 2.3% to 12.5 +/- 3.6%, P less than 0.05) inspired nitrous oxide (gradual administration) and also during abrupt 60% nitrous oxide administration (6.4 +/- 2.6% to 9.9 +/- 3.2%, P less than 0.05). After abrupt 60% inspired nitrous oxide administration, halothane (0.7% inspired) was introduced and caused decreases in mean arterial pressure (106.1 +/- 4.5 mm Hg to 76.2 +/- 5.5 mm Hg, P less than 0.05) and peak LV dP/dt (1700 +/- 150 mm Hg/sec to 1100 +/- 100 mm Hg/sec, P less than 0.05). Halothane caused a marked increase in PSS (9.9 +/- 3.2% to 30.8 +/- 12.6%, P less than 0.05). Thus nitrous oxide administration caused regional dysfunction in myocardium supplied by a critically narrowed LAD whether administered gradually or abruptly and at concentrations as low as 40% inspired.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Histamine antagonists and d-tubocurarine-induced hypotension in cardiac surgical patients.

Hemodynamic effects and histamine release by bolus injection of 0.35 mg/kg of d-tubocurarine were studied in 24 patients. H1- and H2-histamine antagonists or placebo were given before dosing with d-tubocurarine in a randomized double-blind fashion to four groups: group 1--placebo; group 2--cimetidine, 4 mg/kg, plus placebo; group 3--chlorpheniramine, 0.1 mg/kg, plus placebo; and group 4--cimetidine plus chlorpheniramine. Histamine release occurred in most patients, the highest level 2 minutes after d-tubocurarine dosing. Group 1 had a moderate negative correlation between plasma histamine change and systemic vascular resistance (r = 0.58; P less than 0.05) not present in group 4. Prior dosing with antagonists partially prevented the fall in systemic vascular resistance. These data demonstrate that the hemodynamic changes associated with d-tubocurarine dosing are only partially explained by histamine release. Thus prior dosing with H1- and H2-antagonists provides only partial protection.

Blood Pressure↗
PubMed1986

The effect of diazepam on induction of anesthesia with alfentanil.

This study investigated the effect of intravenous diazepam on induction of anesthesia with alfentanil. Forty ASA physical status I and II patients were given one of four treatments: alfentanil 100 micrograms/kg or 200 micrograms/kg, without diazepam or preceded by 0.125 mg/kg diazepam intravenously. Blood pressure, heart rate, respiration, response to verbal command, and movement were assessed for 5 min, and blood was taken for measurement of histamine, epinephrine, and norepinephrine. All ten patients receiving 100 micrograms/kg and five of the ten patients receiving 200 micrograms/kg of alfentanil responded to voice after 5 min, but only one in each group responded when it was preceded by diazepam. There was no rigidity or serious arrhythmias in any patient. Heart rate increased in patients receiving alfentanil alone. Blood pressure increased in those receiving 100 micrograms/kg but not 200 micrograms/kg. In patients given diazepam, tachycardia did not occur, but blood pressure decreased after administration of alfentanil. There were no significant changes in plasma levels of histamine or catecholamines. Five of the six cases of inadequate postoperative ventilation were in patients given diazepam. Despite these effects, diazepam or some other hypnotic agent may be indicated when alfentanil is used for induction.

Adult↗