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Biomedical subjects

S Gelman

Publications and source records attributed to S Gelman.

At least 73 records · Page 4Linked to original sources

Glucagon increases hepatic oxygen supply-demand ratio in pigs.

The present study was performed on eight young pigs to test the hypothesis that glucagon increases hepatic oxygen supply to a greater extent than hepatic oxygen uptake, providing a better hepatic oxygen supply-demand relationship. The experiments were performed under pentobarbital sodium anesthesia and controlled ventilation. Splanchnic blood flow was studied using radioactive microspheres. Glucagon was administered in doses of 1 and 5 micrograms X kg-1 X min-1. During glucagon infusion, hepatic arterial blood flow substantially increased, splenic and pancreatic blood flows increased moderately, while stomach and intestinal blood flows, as well as portal blood flow did not change significantly. Shunting of both 9- and 15-micron spheres through preportal tissues did not change significantly. Oxygen content in arterial or portal venous blood did not change significantly, while it increased in hepatic venous blood by 30%. There were no differences in the effects between the doses of glucagon administered. There was no correlation found between changes in hepatic oxygen supply and cardiac output or blood pressure. The changes observed during glucagon administration resulted in an increase in oxygen delivery to the liver and hepatic oxygen supply-uptake ratio.

Animals↗

Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl.

Hepatic blood flow and the oxygen supply/uptake relation were studied in 19 miniature pigs using labeled microspheres. Changes in hepatic arterial blood flow and portal blood flow, as well as total hepatic blood flow during halothane anesthesia were more closely associated with changes in mean arterial pressure (MAP) and cardiac output than during anesthesia with isoflurane or fentanyl. Halothane or isoflurane administered in concentrations that decreased MAP by approximately 30% were accompanied by decreases in hepatic oxygen delivery (DO2th) averaging 46% during halothane and 31% during isoflurane anesthesia and parallel decreases in hepatic blood flow. In concentrations that decreased MAP by 50%, halothane and isoflurane decreased DO2th 61 and 37%, respectively. DO2th was maintained (statistically insignificant, 23% increase) during both doses of fentanyl administered (20 micrograms/kg followed by 0.17 microgram . kg-1 . min-1, and 50 micrograms/kg followed by 0.42 microgram . kg-1 . min-1). Hepatic oxygen uptake increased 50% during fentanyl and was maintained at baseline levels during both doses of halothane and isoflurane anesthesia. Oxygen content in hepatic venous blood was maintained at baseline levels during fentanyl and isoflurane administration and was decreased by both concentrations of halothane anesthesia. The hepatic oxygen supply demand ratio was maintained at baseline levels after both doses of fentanyl and during isoflurane administered in a concentration that decreased blood pressure 30%; the ratio decreased during isoflurane administered in a concentration decreasing blood pressure by 50% and during both doses of halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Effects of anaesthesia induction drugs on circulation in denervated intestinal loop preparation.

The effect of anaesthesia induction drugs on the intestinal circulation was evaluated in an isolated loop preparation in 28 dogs. Selected intestinal loops were perfused with aortic blood by a pump at a constant pressure of 100 mmHg. A mixture of 86Rb and 9 microns spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal segment while mesenteric venous blood was collected for activity counting. Diazepam in a dose of 3 mg X kg-1 was accompanied by a significantly lower clearance (Cl-Rb), and permeability-surface area product (PS) than pentobarbitone; there were no differences between diazepam and pentobarbitone in total blood flow (BF), vascular resistance (VR) and oxygen consumption in the intestinal segments. Circulatory variable observed after midazolam, 8 mg X kg-1 and an additional 16 mg X kg-1, did not significantly differ from those seen during pentobarbitone. Ketamine in a dose of 8 mg X kg-1 was accompanied by a significantly lower BF, Cl-Rb, microsphere entrapment (Cl-Sph), PS, and higher VR and arterio-venous oxygen content difference. Sixteen mg X kg-1 of ketamine did not lead to any additional changes in determined variables of the intestinal circulation. Alpha-adrenoceptor blockade completely abolished vasoconstriction caused by ketamine, suggesting that the long-lasting vasoconstricting effect of ketamine on the intestinal circulation is mediated through catecholamines.

Anesthesia↗

Intestinal circulation during inhalation anesthesia.

This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86Rb and 9-microns spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-microns spheres through the intestines reflects the arteriovenous shunting of blood. Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO2) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Midazolam pharmacodynamics and pharmacokinetics during acute hypovolemia.

This study was designed to test the hypothesis that acute hypovolemia would compromise the compensatory hemodynamic mechanisms to midazolam and decrease its metabolic clearance. Experiments were performed on seven chronically instrumented female beagle dogs. Animals received a single intravenous dose of midazolam, 10 mg/kg, 4 days apart during normovolemic (N) and hypovolemic (H) states in a random sequence. Hypovolemia was achieved by the withdrawal of 26 ml/kg of blood, equivalent to one-third of the calculated blood volume. Midazolam plasma concentrations were determined at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after midazolam injection. Elimination half-life (t 1/2 beta) was significantly longer and total clearance was significantly lower during H than during N. Initial distribution half-life, central compartment volume, total volume of distribution, and plasma protein binding were similar in both N and H states. Midazolam caused a significant decrease in systolic blood pressure (SBP) and an increase in heart rate (HR) during N, and produced significant decreases in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) during H. Midazolam led to similar per cent decreases in blood pressure and cardiac output in states N and H; however, the absolute values of blood pressure and cardiac output were significantly (P less than 0.001) lower in the hypovolemic state than in the normovolemic state. These data suggest that the hypotensive effects of midazolam, like those of other intravenous induction agents, could be potentiated by volume depletion.

Anesthetics↗

Cardiac output distribution and regional blood flow during hypocarbia in monkeys.

Cardiac output distribution and regional blood flow were studied during hypocarbia independent of changes in ventilatory parameters. Fifteen cynomolgus monkeys were anesthetized with methohexital sodium (8 mg/kg im) and hyperventilated through an endotracheal tube. Hypocarbia at two levels, 28 +/- 1.8 and 17 +/- 0.6 Torr, was achieved by a stepwise decreasing CO2 flow into the semiclosed system. Regional blood flow was determined with labeled microspheres. At each stage of experiments two sets of microspheres (9 and 15 microns diam) were used simultaneously. The use of two microsphere sizes allowed evaluation of the relationship between total (nutritive and nonnutritive) tissue blood flow, determined with 15-microns spheres, and nutritive blood flow, determined with 9-microns spheres. There was no change in cardiac output or arterial pressure during both degrees of studied hypocarbia. Hypocarbia was accompanied by a decrease in myocardial blood flow determined with 15-microns spheres and preservation of the flow determined with 9-microns spheres. Splenic blood flow was decreased, whereas hepatic arterial blood flow was increased during both levels of hypocarbia. Blood flow through the brain, renal cortex, and gut showed a biphasic response to hypocarbia: during hypocarbia at 28 +/- 1.8 Torr, blood flow determined with 15-microns spheres was unchanged (in the gut) or decreased (in the brain and kidneys), whereas blood flow determined with 9-microns spheres was decreased. During hypocarbia at 17 +/- 0.6 Torr, blood flow determined with 9-microns spheres had a tendency to restore to base-line values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of fentanyl and morphine on intestinal circulation.

The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of 86Rb and 9-micron spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O2up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

Animals↗

Renal and splanchnic circulation during infrarenal aortic cross-clamping.

The effect of infrarenal cross-clamping of the aorta on regional splanchnic and renal circulations was studied in seven dogs. Regional blood flow was determined with differentially labeled microspheres (9 and 15 micron in diameter) that were injected simultaneously into the left atrium. Blood flow was measured 30 minutes after surgical preparation was completed (stage I), 20 minutes after infrarenal aortic cross-clamping (stage II), and 20 minutes after supplemented sodium nitroprusside infusion (stage III). Infrarenal aortic cross-clamping was accompanied by a slight increase in the cardiac output (CO) without significant changes in mean arterial pressure (MAP). Blood flow through the gut, hepatic artery, and cortical layer of the kidneys, as determined with 15-micron spheres, was not changed. Nonentrapment of 9-micron spheres in the gut and renal cortex was increased substantially. Blood flow through the juxtamedullary layer of the kidneys was increased. Sodium nitroprusside supplementation decreased MAP by 30%; CO values returned to baseline level. Hepatic artery blood flow, compared with both baseline values and values during aortic cross-clamping, increased significantly. Blood flow, determined with 15-micron spheres, through the gut and renal cortex did not change, and nonentrapment of 9-micron spheres decreased to baseline values. The data suggest a certain shift of blood flow to the juxtamedullary layer of the kidneys during aortic cross-clamping and normalization of intrarenal blood flow distribution during supplemented sodium nitroprusside infusion. Controlled vasoplegia with sodium nitroprusside may help modify peripheral circulatory disturbances in the kidneys and splanchnic system during infrarenal aortic cross-clamping.

Animals↗

Hormonal and haemodynamic responses to upper abdominal surgery during isoflurane and balanced anaesthesia.

The purpose of the study was to compare the protective role of different anaesthetic techniques against surgical stress. Sixty patients undergoing elective laparotomy were randomly divided into six groups of ten patients each: Group I was given 0.65 MAC nitrous oxide (66 per cent inspired) and 0.65 MAC isoflurane (0.75 per cent end-expired); Group II was given 0.65 MAC nitrous oxide and 1-1.2 MAC isoflurane (1.2-1.4 per cent end-expired); Group III was given the same anaesthetic management as patients in Group I but with the addition of fentanyl (2 micrograms X kg-1) before the skin incision and 1/8 of the initial dose every 15 minutes during surgery; Group IV was treated as patients in Group I with an additional infusion of lidocaine (30 micrograms X kg-1 X min-1); Groups V and VI were given 0.65 MAC of nitrous oxide and fentanyl, 7.5 and 15 micrograms X kg-1, respectively, before skin incision with 1/8 of the initial dose every 15 minutes during the operation; diazepam, 5 mg IV each hour of surgery, was given to prevent intraoperative awareness. Cortisol concentration was determined by radioimmunoassay method and catecholamines were measured by high performance liquid gas chromatography in blood samples taken at different stages perioperatively. All patients had satisfactory haemodynamic courses of anaesthesia. Statistically significant increases in both epinephrine and norepinephrine concentrations were observed during the immediate postoperative period in Group I patients only. Haemodynamic stability was maintained despite a two- to three-fold increase in cortisol which occurred during the operation and immediate postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Liver circulation and function during isoflurane and halothane anesthesia.

Hepatic arterial blood flow (HABF) and portal blood flow (PBF) were measured in 18 dogs while awake and during isoflurane and halothane anesthesia. Surgical preparation 1 week before the measurements consisted of a left thoracotomy, placement of a left atrial catheter, and insertion of another catheter into the distal aorta via the left femoral artery. Cardiac output and liver blood flow were determined using microspheres at three stages: stage 1-awake state; stage 2-after 45 min of 1 MAC of isoflurane (eight dogs) or halothane (10 dogs) anesthesia; and stage 3-after 45 min of 2 MAC of inhalation anesthesia. Half-life and fractional clearance for indocyanine green (ICG) were determined 1 day before the experiment (awake state), and at the end of stages 2 and 3. Mean arterial pressure (MAP) and cardiac index (CI), as well as PBF, decreased during isoflurane and halothane anesthesia. HABF increased significantly during isoflurane anesthesia, remained unchanged during 1 MAC of halothane anesthesia, and significantly decreased during 2 MAC of halothane anesthesia. Apparently, hepatic oxygen supply was maintained much better during isoflurane than during halothane anesthesia. PBF correlated with CI during halothane (r = 0.97) and, to a certain extent, with MAP during isoflurane (r = 0.66). HABF correlated with CI and MAP during halothane (r = 0.74 and 0.71, respectively) but did not correlate with systemic hemodynamic variables during isoflurane. ICG half-life significantly increased during 1 and 2 MAC of halothane anesthesia. The degree of increase did not correlate with the level of anesthesia or the decrease in total hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗