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Biomedical subjects

R G Merin

Publications and source records attributed to R G Merin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. VI. Verapamil and fentanyl-pancuronium.

To assess the interaction between verapamil and fentanyl-pancuronium, dogs were chronically instrumented to measure heart rate; PR interval; aortic, left ventricular, and left atrial pressures; and coronary, carotid, and renal blood flows. The effect of fentanyl citrate infusion on single-dose verapamil pharmacokinetics was examined in six animals. The effects of verapamil infusion (3 micrograms.kg-1.min-1 and 6 micrograms.kg-1.min-1) were examined in the conscious state and during fentanyl infusion plus pancuronium on two separate occasions in nine dogs. In addition, the effects of fentanyl citrate (500 micrograms.kg-1 followed by 1.5 micrograms.kg-1.min-1) were examined over 1 h of infusion. Fentanyl infusion did not affect single-dose verapamil pharmacokinetics. In the conscious animals, verapamil increased heart rate and PR interval, and slightly decreased LV dP/dt. Fentanyl combined with pancuronium increased mean arterial pressure and LV dP/dt. During fentanyl infusion, verapamil decreased mean arterial pressure and LV dP/dt, increased PR interval, and did not change heart rate. The hemodynamic effects of fentanyl infusion were steady over 1 h. In contrast to the inhalational anesthetics, which alter verapamil pharmacokinetics and have mainly additive effects with verapamil on left ventricular contractility, cardiac conduction, and regional blood flows, fentanyl-pancuronium had no effect on verapamil pharmacokinetics and minimal effect on verapamil pharmacodynamics in healthy dogs.

Animals↗
PubMed1988

Effect of halothane on glucose utilization in the perfused working rat heart.

To define the mechanism of the cardiodepressant action of halothane, we used the perfused working rat heart to study the effects of the anesthetic on glucose utilization and left ventricular function, both in the absence and presence of insulin. Rates of glucose utilization were measured by the appearance of 3HOH in the coronary effluent derived from 2-3H-glucose added to the media. Lactate production was determined by enzymatic methods. Tissue glycogen was measured by enzymatic methods to calculate total glucose available for energy production by the heart. Halothane, up to 2.4% concentration, had a dose dependent depressant effect on oxygen consumption, mechanical performance, and utilization of media glucose. Exogenous insulin did not affect this relation. Glycogen stores decreased in the presence of halothane and control values were not preserved by the presence of insulin. Lactate production was depressed by halothane in the absence of insulin and was unchanged in the presence of insulin. The ratio of glycolysis to oxygen consumption was increased by halothane both in the presence and absence of insulin. This disparate effect on glucose metabolism, compared with function, may be explained by an inhibition of pyruvate dehydrogenase.

Animals↗
PubMed1988

Functional and metabolic effects of bupivacaine and lidocaine in the perfused working rat heart.

The effects of bupivacaine (2.5, 5, 10, and 12.5 mg/L) and lidocaine (12.5, 25, 40, and 50 mg/L), on spontaneous heart rate, mean pressure development, cardiac output, and coronary flow were compared after 15 minutes' exposure in the isolated perfused working rat heart preparation. In addition, myocardial oxygen consumption, glucose utilization, lactate production, tissue content of glycogen, adenine nucleotides, and creatine phosphate content were measured. The relative potency of bupivacaine to lidocaine, calculated from slopes of regression equations, as indicated by the four mechanical variables and oxygen consumption, was 4.59. When the bupivacaine concentration was "normalized" using this value, bupivacaine and lidocaine showed indistinguishable effects on glucose utilization, lactate production, and tissue glycogen. Neither of the local anesthetics had any influence on energy charge or creatine phosphate content.

Animals↗
PubMed1987

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. IV. Chronically administered oral verapamil and halothane, enflurane, and isoflurane.

Dogs were chronically instrumented to measure aortic and left atrial blood pressures, left ventricular maximal rate of tension development (dP/dt), cardiac output, and carotid, coronary and renal blood flows. Measurements were taken with the animals awake and during steady-state low and high concentrations of halothane (1.2%, 2.4%), enflurane (2.4%, 4.0%), and isoflurane (1.6%, 3.0%) with and without at least 2 weeks of oral verapamil, 120 mg, three times per day. Plasma verapamil levels varied widely, with means of 500-700 ng X ml-1 in awake animals and lower (300-400 ng X ml-1) at the time of hemodynamic measurements during anesthesia. Chronic oral verapamil in awake dogs produced predominantly tachycardia. The hemodynamic effects of low-dose halothane and isoflurane before and after oral verapamil were unchanged except for decreased renal blood flow after oral verapamil and no coronary vasodilation nor tachycardia. However, left atrial pressure was increased and cardiac output and coronary blood flow were decreased by low concentrations of enflurane with oral verapamil compared to without. The combination of oral verapamil with low (clinical) doses of enflurane was more depressant to the cardiovascular system of healthy dogs than was the combination of verapamil and halothane or isoflurane.

Administration, Oral↗
PubMed1987

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics.

To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1987

Role of isoflurane on hemodynamic properties and disposition of nicardipine.

Nicardipine properties (30 micrograms/kg i.v.) were studied in a group of eight dogs awake and anesthetized with isoflurane 1.6% end-tidal. Awake, nicardipine produced a decrease in mean arterial pressure (-12 +/- 2 mm Hg) associated with an increase in cardiac output (1.63 +/- 0.2 liters/min), heart rate (75 +/- 9 beats/min), dP/dt (741 +/- 202 mm Hg/sec) and carotid (41 +/- 11 ml/min) and coronary blood flows (39 +/- 6 ml/min). During isoflurane, responses to nicardipine injections were less pronounced except for mean arterial pressure (-19 +/- 2 mm Hg) and reversed for dP/dt (-290 +/- 63 mm Hg/sec). In a second group of six conscious dogs, nicardipine (30 micrograms/kg i.v.) injected after ganglionic blockade (chlorisondamine, 2 mg/kg i.v.) elicited changes similar to those recorded during isoflurane anesthesia, data that demonstrated the importance of isoflurane-induced baroreflex blockade as a mechanism of the pharmacodynamic interactions between nicardipine and isoflurane. Isoflurane reduced nicardipine initial volume of distribution (11.6 +/- 1.2 vs. 8.9 +/- 0.8 liters), total clearance (28.5 +/- 2.9 vs. 19.2 +/- 2.1 liters/hr) and volume of distribution at steady state (50.0 +/- 11.3 vs. 29.2 +/- 3.7 liters, P less than .05). Nicardipine-induced hemodynamic changes were linearly correlated with the drug concentrations in plasma. In the presence of isoflurane, the slopes of these relationships were reduced for all hemodynamic variables except for mean arterial pressure, for which the slope was more pronounced, and dP/dt, for which the slope was reversed. In conclusion, isoflurane alters the drug plasma concentration-effect relationship of nicardipine as a result of both pharmacokinetic and pharmacodynamic interactions.

Animals↗
PubMed1987

Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil.

Lidocaine (3 mg/kg i.v.) injected during steady-state verapamil infusions (3 micrograms/kg i.v.) induced slight and transient hemodynamic changes in nine conscious dogs. Systemic vascular resistance and left ventricular dP/dt decreased by 16% from 41 +/- 4 mm Hg/liter/min and by 20% from 2876 +/- 137 mm Hg/sec, respectively, whereas heart rate and cardiac output increased by 18% from 100 +/- 5 beats/min and by 17% from 2.5 +/- 0.2 liters/min, respectively. Simultaneously, lidocaine induced a transient but more pronounced decrease in verapamil plasma concentration of 48% from 60 +/- 3 ng/ml. This pharmacokinetic interaction was not the result of a lidocaine-induced decrease in the fraction of verapamil bound to plasma protein because in vitro lidocaine failed to displace verapamil from its protein binding site. Moreover, an increase in verapamil total clearance was not the only mechanism because steady-state lidocaine (6 mg/kg over 5 min followed by 60 micrograms/kg/min) in the presence of steady-state verapamil (200 micrograms/kg over 3 min followed by 3 micrograms/kg/min) also resulted in a transient decrease in verapamil plasma concentration from 59 +/- 9 to 23 +/- 2 ng/ml in six conscious dogs. Although verapamil did not affect lidocaine pharmacokinetics, in the presence of the steady-state lidocaine we recorded an increase in verapamil initial volume of distribution of 44% from 40 +/- 4 liters, and intercompartmental clearance increased by 88% from 101 +/- 20 liters/hr, combined with an increase in verapamil total clearance of 47% from 54 +/- 6 liters/hr (n = 6).

Animals↗
PubMed1987

Hepatic dysfunction after isoflurane anesthesia.

Four members of the Anesthetic and Life Support Advisory Committee of the Food and Drug Administration assessed the contribution of isoflurane (Forane) to 45 instances of hepatic dysfunction after isoflurane anesthesia reported to the FDA for 1981-1984. For 29 (64%) of the cases, at least three members concluded that nonanesthetic causes (e.g., hypoxia, sepsis, viral infection) explained the hepatic injury. For 16 cases (36%), two or more members concluded that isoflurane might be one of several possible causes of the hepatic injury. In the latter cases, patients tended to be younger, had undergone anesthesia of shorter duration for operations outside the chest and abdomen, had developed symptoms later, had higher plasma transaminase values but lower bilirubin values, and had a lower incidence of eosinophilia, anemia, transfusions, and congestive heart failure. The committee concluded that current evidence does not indicate a reasonable likelihood of an association between the use of isoflurane and the occurrence of postoperative hepatic dysfunction.

Adolescent↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. I. Verapamil and halothane.

In order to assess the interaction between halothane and verapamil on the cardiovascular system, mongrel dogs were instrumented so that the following measurements could be made awake and under the influence of the drugs: aortic, left ventricular, and left atrial blood pressures; myocardial segment length shortening; heart rate and rhythm; and coronary, carotid, and renal blood flows. The effect of two infusion doses of verapamil (3 micrograms X kg-1 X min-1 and 6 micrograms X kg-1 X min-1 after 200 micrograms X kg-1 bolus) were examined awake. On a different day in the same dogs, two concentrations of halothane (1.2-low and 2.4-high % end-tidal) and the effect of the two infusion doses of verapamil during low and high halothane were studied. Thirty minutes of either infusion dose of verapamil produced only heart rate and electrocardiographic P-R interval increases in conscious dogs. Halothane produced dose-related decreases in mean aortic pressure, left ventricular maximum rate of tension development (dP/dt), and segment length shortening and increases in heart rate and left atrial pressure. Carotid blood flow was increased by low halothane concentrations and returned to control with high halothane concentrations. There were no significant changes in coronary or renal blood flow produced by halothane. Verapamil infusion during low halothane concentration produced minimal effects. However, both the 3 and 6 micrograms X kg-1 X min-1 verapamil doses further depressed hearts already depressed by the high concentrations of halothane and decreased renal and carotid blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. II. Verapamil, enflurane, and isoflurane.

The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. III. Nicardipine and isoflurane.

To assess the interaction between isoflurane and the new calcium channel blocker, nicardipine, mongrel dogs were chronically instrumented to allow the following measurements: aortic, left ventricular and left atrial pressures; heart rate; cardiac output; and carotid, coronary, and renal blood flows. The hemodynamic effects of intravenous nicardipine 5, 10, 30, and 50 micrograms/kg were measured in awake dogs and during 1.6 and 3.0 per cent (end-tidal) isoflurane anesthesia. Nicardipine induced a dose-dependent fall in mean arterial pressure in both awake dogs and during 1.6 and 3.0 per cent isoflurane anesthesia. Heart rate and cardiac output were increased in proportion to the nicardipine dose in the awake dogs and, to a lesser degree, in the dogs anesthetized with 1.6 per cent isoflurane, but did not change during 3.0 per cent isoflurane anesthesia. Left atrial pressure was unchanged by nicardipine in awake dogs and during anesthesia. Left ventricular maximum rate of tension development (dP/dt) increased in awake dogs and decreased during anesthesia. Coronary blood flow increased dose dependently without anesthesia, and, to a smaller degree, during anesthesia. Nicardipine increased carotid blood flow without anesthesia, whereas it was unchanged during anesthesia. Renal blood flow was unchanged in awake dogs and decreased during anesthesia. The authors conclude that nicardipine is a potent vasodilator that minimally affects cardiac function and regional blood flow in the presence of isoflurane. The interactions between nicardipine and isoflurane are mainly the result of the isoflurane-induced inhibition of the reflex tachycardia elicited by nicardipine.

Animals↗
PubMed1986

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs.

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗