Biomedical subjects

H J Fontenot

Publications and source records attributed to H J Fontenot.

9 recordsLinked to original sources

PubMed1999

Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness.

UNLABELLED: Propofol (iv) depresses cardiovascular function in both humans and animals. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that this effect of propofol results in part from an antagonism of adrenergic control of the heart. Experiments examined effects of propofol on: 1) [3H]CGP12177 (a beta-adrenoceptor antagonist) binding in rat myocardial membranes; and 2) the inotropic and chronotropic actions of isoproterenol in rat left atrial muscle and right atria, respectively. Propofol (25-200 microM) increased the apparent dissociation constant for [3H]CGP12177 without affecting binding site density. Similarly, 200 microM propofol increased the 50% effective concentration values for the dose-dependent positive chronotropic and inotropic actions of isoproterenol in right and left atria, and depressed the maximum increase in spontaneous rate elicited by this beta-adrenoceptor agonist. Other experiments demonstrated that propofol does not alter muscarinic receptor binding as monitored using [3H]quinuclidi-nylbenzilate. In conclusion, these results indicate that propofol can decrease cardiac beta-adrenoceptor responsiveness; however, the concentrations of propofol required suggest that this action contributes to the cardiovascular depression produced by this anesthetic only during large-dose bolus injection. IMPLICATIONS: Experiments in membranes and cardiac preparations isolated from rat heart demonstrate that relatively high concentrations of propofol (25-200 microM) are required to antagonize beta-adrenoceptor binding and tissue responsiveness.

Adrenergic beta-Agonists↗

PubMed1998

An algorithm to optimize perioperative blood management in surgery.

Innovation in surgical blood management has been fueled by patients' perceptions of the risks associated with allogeneic blood transfusions and by surgeons' attitudes toward the use of allogeneic blood. The challenge is to determine the best blood management strategy to implement in the individual patient, particularly in patients with anemia who are at high risk of allogeneic blood transfusion. An algorithm to estimate safe blood loss based on individual patient parameters has been developed. The algorithm uses patient weight, gender, and preoperative hematocrit level to derive the volume of blood loss that can be tolerated while maintaining a target postoperative hematocrit level. Because the margin of safe blood loss can be anticipated, the most appropriate blood conservation option(s) can be implemented and perioperative blood management can be optimized.

Algorithms↗

PubMed1997

Alpha 1D-adrenoceptors play little role in the positive inotropic action of phenylephrine.

This study was designed to determine if the positive inotropic action of alpha 1-adrenergic stimulation in rat heart is mediated via alpha 1D-adrenoceptors. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 1 microM nadolol and paced at 3.0 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine were obtained in the presence and absence of BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5] decane-7,9-dione), a selective competitive alpha 1D-adrenoceptor antagonist. BMY 7378 at concentrations up to 30 nM did not significantly affect the positive inotropic response to phenylephrine. In contrast, as reported by other investigators, alpha 1D-adrenoceptor-selective concentrations of this antagonist (3 and 10 nM) did elicit a concentration-dependent right-ward shift in the vasoconstrictor response to phenylephrine in rat abdominal aorta. These data suggest that alpha 1D-adrenoceptors do not play a major role in the positive inotropic action of alpha-adrenoceptor stimulation in rat cardiac muscle.

Adrenergic alpha-Agonists↗

PubMed1997

Modulation of cardiac calcium channels by propofol.

BACKGROUND: Propofol elicits a rapid depression of transsarcolemmal Ca2+ influx and myocardial contractility. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that propofol acts as an antagonist of L-type calcium channels. METHODS: Experiments monitored effects of propofol on (1) the binding of [3H]nitrendipine (a 1,4-dihydropyridine calcium channel antagonist) to rat myocardial membranes; (2) L-type calcium current (ICa,L) as determined using whole-cell patch-clamp techniques in intact rat cardiomyocytes; and (3) myocardial contractility as examined in isolated rat papillary muscle. RESULTS: Propofol, in concentrations as low as 6 microM, increased the apparent dissociation constant (Kd) for [3H]nitrendipine without affecting binding-site density (Bmax). This decrease in dihydropyridine-binding affinity was associated with a depressed ICa,L in cardiomyocytes and diminished myocardial contractility. Other experiments showed that etomidate has no effect on [3H]nitrendipine binding, whereas ketamine enhances dihydropyridine binding. CONCLUSION: Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.

Animals↗

PubMed1996

Effects of aging on Na(+)-pump current in rat ventricular myocytes.

This study was designed to determine if aging affects ouabain-sensitive Na(+)-pump current (Ip), an electrophysiological measure of Na,K-ATPase activity, in rat heart. Ventricular myocytes were enzymatically isolated from hearts of young adult (4-6 months of age) and aged (28-36 months of age) male Long-Evans rats. Ip was monitored using conventional whole-cell patch-clamp techniques under both maximally stimulating (85 mM intracellular Na+ with 10.8 mM extracellular K+) and 'physiological' (10 mM intracellular Na+ with 5.4 mM extracellular K+) conditions. Values were expressed relative to membrane capacitance to account for the larger cell size of the aged myocytes. Results indicated that maximal Ip is smaller (e.g. approximately 23% at the holding potential of -40 mV) in myocytes isolated from aged as compared to young adult rats. However, neither the voltage-dependence of maximal Ip nor the pump current monitored under 'physiological' conditions were affected by age in general, these data support results of previous biochemical and ion flux studies which demonstrated that aging is associated with a decline in the Na(+)-pump capacity of the myocardium.

Aging↗

PubMed1996

The comparative effects of sevoflurane versus propofol in the induction and maintenance of anesthesia in adult patients.

A randomized, prospective study was performed at four institutions to compare anesthetic induction, maintenance, and recovery characteristics between sevoflurane- and propofol-based anesthesia in 186 ASA physical status I and 11 patients undergoing elective surgical procedures of 1-3 h. Group 1 (n = 93) patients received sevoflurane-nitrous oxide for both induction and maintenance of anesthesia while Group 2 (n = 93) received propofol-nitrous oxide anesthesia. Induction of anesthesia and tracheal intubation times were significantly shorter with propofol (2.21 +/- 0.2 min, 5.11 +/- 0.3 min, respectively) than with sevoflurane (3.11 +/- 0.2 min, 7.21 +/- 0.3 min, respectively). Emergence times after sevoflurane (8.81 +/- 1.2 min) were significantly shorter than with propofol (13.21 +/- 1.2 min). Overall frequency of complication-free induction, maintenance, and emergence did not differ between the two anesthetic groups. However, side effects involving airway excitement were more prevalent during mask induction with sevoflurane as compared to propofol. Patients in the sevoflurane group were oriented and required postoperative analgesia much earlier than those who received propofol. Both groups were hemodynamically stable throughout the study period. The incidence of postoperative nausea, vomiting, and pain-discomfort scores were similar between the two groups. Urinary specific gravity decreased in the sevoflurane-treated group while serum creatinine and urinary pH were unchanged from preoperative values in both groups. Sevoflurane compared favorably with propofol when used for anesthesia for elective procedures of 1-3 h duration.

Adult↗

PubMed1995

Ten strategies to reduce blood loss in orthopedic surgery.

In any operative procedure, careful surgical dissection with precise hemostasis is one of the most effective ways to minimize surgical blood loss and reduce the need for allogeneic red blood cell transfusion. Several other techniques contribute to reduce blood loss in major orthopedic procedures. These techniques are reviewed and include rehearsal of the procedure and positioning the patient to reduce venous engorgement. In addition, a case report is presented that demonstrates the feasibility of revision hip replacement surgery without the use of transfusion in a Jehovah's Witness patient.

Adolescent↗

PubMed1995

Tetramethylammonium is a muscarinic agonist in rat heart.

Studies were designed to determine if tetramethylammonium (TMA), a quaternary amine that structurally resembles the cationic portion of acetylcholine, can affect cardiac function by acting on muscarinic receptors. Experiments examined effects of this cation on 1) the spontaneous beating rate of right atrial preparations isolated from rats, 2) force of contraction in isoproterenol-treated (0.1 microM) rat papillary muscle, and 3) quinuclidinyl benzilate ([3H]QNB) binding to rat ventricular membranes. TMA elicited concentration-dependent (0.5-50 mM) negative chronotropic and negative inotropic actions that were antagonized by the muscarinic receptor antagonist atropine. Radioligand studies showed that TMA acts as both a competitive and noncompetitive antagonist of [3H]QNB binding; the apparent dissociation constant for [3H]QNB was increased (0.092 +/- 0.025 nM in the absence of TMA; 1.14 +/- 0.204 nM in the presence of 50 mM TMA), whereas binding site density was decreased (148 +/- 26 and 65 +/- 4 fmol/mg in the absence and presence of 50 mM TMA, respectively). These results suggest that extracellular TMA can alter the function of rat heart by stimulating muscarinic receptors. This action should be considered when using this quaternary amine as a cation substitute.

Animals↗

PubMed1985

The prolonging effect of N,N'-diallylpentobarbital on the drug-induced sleep and motor incoordination.

N-Allyl substituted derivatives of pentobarbital were prepared, and their pharmacological activities (hypnotic activity and anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures) were investigated with single intraperitoneal (i.p.) injection using mice. N-Monoallylpentobarbital (MAPB) was found to possess hypnotic activity [HD50 = 77.5(64.3-93.4) mg/kg, i.p.] and anticonvulsant activity [PTZ-ED50 = 23.5(14.2-38.9)mg/kg, i.p.]. N,N'-Diallylpentobarbital (DAPB) was devoid of not only the hypnotic activity of parent compound but also the anticonvulsant activity. The interaction of these N-allyl derivatives with barbiturates (pentobarbital (PB), barbital (B), phenobarbital (PheB), amobarbital (AB) and thiopental (TP] or diazepam (DZ) was further studied to characterize as antagonist or agonist. MAPB and DAPB (5-160mg/kg, i.p.) showed potent prolonging effect on PB-induced sleeping time and time of their peak effect was observed. The prolonging effects of these allyl compounds on PB-induced sleep were dose-dependent. Both compounds (80mg/kg, i.p.) also prolonged sleeping time induced by PheB, AB and TP. Although DAPB showed prolonging effect on B-induced sleep at a time interval 1 min, the compound shortened the sleeping time at 15 and 60 min. DAPB (5, 10 and 80mg/kg, i.p.) enhanced the DZ-induced motor incoordination.

Animals↗