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Biomedical subjects

S Gelman

Publications and source records attributed to S Gelman.

At least 19 recordsLinked to original sources

Angiotensin and adrenoceptors in the hemodynamic response to aortic cross-clamping.

This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.

Adrenergic alpha-Antagonists

Haemodynamic changes and oxygen uptake during crossclamping of the thoracic aorta in dexmedetomidine pretreated dogs.

This study was designed to test the hypothesis that the alpha 2 adrenergic agonist, dexmedetomidine (DEX), decreases tissue oxygen demand thereby increasing tolerance to hypoxic insult. In 17 anaesthetized dogs, cardiac output was measured with thermodilution, blood flow through the inferior caval vein was determined using an electromagnetic flowmeter, and oxygen consumption was calculated by the Fick principle. The animals were divided into three groups: control group (n = 5), D3 and D30 groups (n = 6 for each group) treated with two doses of DEX (3 micrograms.kg-1 and 30 micrograms.kg-1, respectively) prior to aortic crossclamping. Upon crossclamping of the thoracic aorta, the cardiac index decreased in all three groups with the largest decrease in the D30 group, and the smallest decrease in the control group. Blood flow through the inferior vena cava decreased in all three groups of animals while blood flow through the superior caval vein increased in the control group, did not change in the D3 group, and decreased in the D30 group. Oxygen saturation in mixed venous blood increased in the control group, did not change in the D3 group and decreased in D30 group. Blood flow and oxygen uptake in the lower part of the body decreased in all groups. Oxygen consumption in the upper part of the body decreased equally in all three groups. Arterial lactate concentrations increased almost two-fold in the control group while it increased by only 30% in animals treated with DEX. A lesser increase in lactate concentrations and oxygen extraction in tissues below aortic crossclamping is consistent with the hypothesis that DEX decreases tissue oxygen requirement which might prove particularly useful in clinical situations where tissue hypoxia is expected.

Adrenergic alpha-Agonists

H1 and H2 receptor antagonists and hepatic oxygen supply-demand relationship in pigs.

The hypothesis that histamine receptor (H1 and H2) blockade beneficially affects the hepatic oxygen supply-demand relationship was tested during experiments performed on 13 miniature pigs. Hepatic arterial and portal blood flows were measured with electromagnetic flowmeters. Cardiac output was determined by thermodilution. H1 and H2 receptor blockade was achieved with promethazine, 5 mg.kg-1 and cimetidine 30 mg.kg-1 IV, respectively. The study demonstrated no significant effect of H1 and H2 receptor blockade on hepatic oxygen uptake and no noticeable effects of cimetidine on hepatic circulation. However, promethazine decreased total hepatic blood flow, primarily by decreasing portal blood flow; this resulted in an increase in oxygen extraction as reflected in a decreased oxygen content in hepatic venous blood. The results reject the posed hypothesis: H1 receptor antagonist promethazine decreased, while H2 receptor antagonist cimetidine did not affect hepatic blood flow and oxygen supply; hepatic oxygen demand remained unaffected during H1 and H2 receptor blockade.

Animals

Humoral factors and hemodynamics during cross-clamping of the thoracic aorta.

The present study was designed to test the hypothesis that vasoactive compounds produced in the ischemic part of the body below an occluded aorta are responsible for the hemodynamic changes observed during cross-clamping of the thoracic aorta. The experiments were performed on 32 rabbits anesthetized with halothane that underwent experiments with cross-circulation; the blood from the inferior caval veins of rabbits A was pumped into the inferior caval veins of rabbits B. Simultaneously, exactly the same amount of blood was pumped from the jugular vein of rabbits B into the jugular vein of rabbits A. The aorta and inferior vena cava were exposed and then simultaneously cross-clamped directly below the diaphragm. The cross-clamping of the aorta and inferior vena cava in rabbits A was associated with a 29% to 44% increase in mean arterial pressure in rabbits B. The experiments support the hypothesis and suggest that endogenously produced humoral factors are responsible for at least one third to one half of the arterial hypertension that usually develops during aortic cross-clamping.

Anesthesia, Inhalation

Hepatic oxygen supply-uptake relationship and metabolism during anesthesia in miniature pigs.

The study evaluated the effects of different anesthetics on the hepatic oxygen supply-demand relationship and hepatic lactate uptake (HLu). Miniature pigs (n = 33), weighing 20-31 kg, were divided into five groups and accordingly anesthetized with halothane, isoflurane, enflurane (0.9%, 1.5%, and 2.2% end-expired concentrations, respectively), fentanyl (100 micrograms/kg iv bolus followed by a continuous infusion of 50 micrograms.kg-1.h-1), or sodium pentobarbital (30 mg/kg iv bolus followed by a continuous infusion at a rate of 1-2 mg.kg-1.h-1). The surgical preparation allowed the authors to induce a stepwise decrease in hepatic blood supply without congestion in the preportal tissues. Prior to induced hepatic hypoperfusion, the values of hepatic oxygen delivery (HDO2) were the greatest in the isoflurane and fentanyl groups and the smallest in the halothane group, while the values of hepatic oxygen uptake (HVO2) were the smallest in the halothane group without differences among the other four groups. During stepwise decrease in hepatic blood and oxygen supply, HLu started to decrease at higher values of hepatic oxygen delivery in the fentanyl group (HDO2 = 10 mlO2.min-1.100 g-1) than in all others (HDO2 = 6-7 mlO2.min-1.100 g-1). At values of HDO2 equal to 2-3 mlO2.min-1.100 g-1, the values of HLu became negative, signifying that the liver began to release rather than to metabolize lactate. There was a linear relationship between the values of HDO2 and hepatic venous oxygen tension or saturation (r = 0.96; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation

Dopamine and hepatic oxygen supply-demand relationship.

The present study examined the effect of small, vasodilating doses of dopamine on the hepatic oxygen supply--uptake ratio. Thirteen miniature pigs weighing 18-27 kg were studied under sodium pentobarbital anesthesia. Hepatic arterial and portal blood flows were measured. Oxygen content in arterial, portal, and hepatic venous blood was determined. Dopamine was infused in doses of 5, 10, and 15 micrograms.kg-1.min-1. Dopamine infusion was associated with a dose-related increase in hepatic oxygen uptake and a dose-independent increase in hepatic oxygen delivery with a maximal increase (30%) in the hepatic oxygen delivery at 10 micrograms.kg-1.min-1. The hepatic oxygen delivery--uptake ratio remained unchanged during dopamine infusion in doses of 5 and 10 micrograms.kg-1.min-1 and significantly decreased during the dose of 15 micrograms.kg-1.min-1. The study demonstrated that an increase in cardiac output and hepatic oxygen delivery during dopamine administration was not associated with an improvement in hepatic oxygen supply--demand relationship since hepatic oxygen uptake also increased.

Animals

Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs.

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.

Animals

Angiotensin and alpha-adrenoceptor activation play a role in hemodynamic response to aortic cross-clamping.

This study was designed to identify the possible role of vasoconstricting compounds released from ischemic tissues in the hemodynamic response to cross-clamping of the thoracic aorta. Twenty-one dogs were anesthetized with pentobarbital sodium. The left hindlimb was denervated, vascularly isolated, and pump perfused at a constant rate with blood drained from the inferior vena cava after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were maintained within normal limits. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 33-45% increase in limb vascular resistance in denervated control animals (n = 6). In animals pretreated with Enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change significantly. In animals pretreated with phenoxybenzamine (3 mg/kg, n = 6), an alpha-adrenoceptor antagonist, limb vascular resistance significantly decreased to 43% of preclamped level. The study demonstrated that vasoconstrictive compounds, such as angiotensin and catecholamines, play a role in systemic hemodynamic changes, including arterial hypertension, observed during cross-clamping of the thoracic aorta.

Angiotensin II

Hepatic circulation and oxygen supply-uptake relationships after hepatic ischemic insult during anesthesia with volatile anesthetics and fentanyl in miniature pigs.

The objective of the present study was to quantitate the effects of several anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult and during reperfusion. We examined the effects of different anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult in 28 miniature pigs weighing 20-27 kg. The preparation allowed a stepwise decrease followed by a complete cessation for 1 h of hepatic blood and oxygen supply. Immediately after the unclamping of both vessels supplying the liver and restoration of the hepatic circulation, systemic mean arterial pressure decreased to approximately 75% of preischemic values in animals anesthetized with pentobarbital and fentanyl and to 60% of preischemic values in pigs anesthetized with halothane, enflurane, or isoflurane. Total hepatic blood flow immediately returned to preischemic values without significant difference between the groups. Subsequently, hepatic oxygen delivery returned to 75%-95% of preischemic values. Hepatic oxygen uptake returned to 50%-60% of preischemic values in animals anesthetized with pentobarbital and with volatile anesthetics and up to 80% and then later to baseline values with fentanyl anesthesia. Lactate uptake by the liver returned to preischemic values only in animals given fentanyl or isoflurane but remained at approximately 50% of preischemic values during enflurane and 20%-40% during halothane and pentobarbital anesthesia. Thus, the study indicates that both isoflurane and fentanyl anesthesia provide more protection from ischemic insult than do halothane, enflurane, or pentobarbital anesthesia.

Anesthetics

Hemodynamics and oxygen uptake below and above aortic occlusion during crossclamping of the thoracic aorta and sodium nitroprusside infusion.

The effects of controlled vasodilation on blood flow and oxygen consumption above and below the aortic occlusion during crossclamping of the thoracic aorta were examined in 16 mongrel dogs anesthetized with halothane. Blood flow in the inferior vena cava was measured with an electromagnetic cannulating flow probe, and cardiac output was measured by thermodilution. The animals were divided into two groups. In the control group the thoracic aorta was crossclamped at the diaphragmatic level for 30 minutes. In the sodium nitroprusside group the aorta was also crossclamped for 30 minutes, but an infusion of sodium nitroprusside was initiated after 10 minutes of occlusion to decrease systemic blood pressure. Measurements were made before and at 10, 20, and 30 minutes after aortic crossclamping, and at 10 minutes after aortic unclamping. Crossclamping of the thoracic aorta was associated with marked decreases in blood flow and oxygen consumption in organs and tissues below the aortic occlusion in both groups. Above the occlusion, blood flow increased but oxygen uptake decreased. Sodium nitroprusside increased cardiac output and blood flow above the aortic occlusion even more than crossclamping alone while it decreased blood flow and oxygen consumption below the crossclamp.

Animals

Circulatory responses to laryngoscopy: the comparative effects of placebo, fentanyl and esmolol.

The circulatory response to a 30-second laryngoscopy followed by orotracheal intubation was recorded in 60 patients of ASA physical status III or IV undergoing a variety of non-cardiac surgical procedures. Patients were randomly allocated to either the placebo, esmolol (500 micrograms.kg-1.min-1 X 6 minutes, followed by 300 micrograms.kg-1.min-1 X 9 minutes), or fentanyl (0.8 microgram.kg-1.min-1 X 10 minutes) group, and the observer was blinded to the infusion administered. Esmolol blunted the heart rate (HR) response, while fentanyl decreased it below the baseline and maintained it there, in spite of laryngoscopy. Similarly, fentanyl decreased the systolic (SBP), mean (MBP) and diastolic blood pressures (DBP) significantly below the baseline, while these pressures were either retained at or elevated slightly above control in the esmolol group. In these doses, the HR response to laryngoscopy was more effectively blocked by fentanyl, while esmolol better retained perfusion pressure. There were no complications or ischaemic electrocardiographic changes in any patient.

Adrenergic beta-Antagonists

Anaphylactoid reactions to vascular graft material presenting with vasodilation and subsequent disseminated intravascular coagulation.

This report describes five patients who had immediate adverse reactions following placement of a vascular graft. All had unusually persistent decreases in systemic vascular resistance, and four of these patients had bleeding as an early manifestation of this reaction. In two of three patients in whom the graft was replaced, uneventful recovery followed. Both patients in whom the graft was not replaced died. Blood samples from two of the patients demonstrated activation of complement and of the kinin system, whereas control patients did not demonstrate increased levels of activation products from these cascade systems. Recognition of this syndrome is important to patient survival, which appears to depend on rapid replacement of the graft.

Aged

Hemodynamic changes and oxygen consumption in burned patients during enflurane or isoflurane anesthesia.

The effects of enflurane or isoflurane anesthesia on the systemic circulation and whole-body oxygen (O2) uptake (VO2) of 15 burn patients undergoing wound excision and skin grafting procedures were studied. The possibility that burn wound excision might adversely affect pulmonary circulation was also investigated. The patients were preanesthetically in a hyperdynamic-hypermetabolic state, characterized by a resting cardiac index (CI) of 6.2 +/- 0.9 L.min-1.m-2 (mean +/- SD), a VO2 (calculated using the Fick principle) of 213 +/- 44 mL.min-1.m-2, a normal mean systemic arterial pressure (MAP) (92 +/- 15 mm Hg), and markedly decreased systemic vascular resistance (SVR) (570 +/- 162 dynes.sec.cm-5). Mean pulmonary arterial pressure (MPAP) preanesthetically was slightly increased (21 +/- 3 mm Hg), while pulmonary vascular resistance (PVR) was in the low-normal range (59 +/- 16 dynes.sec.cm-5). No difference among the effects of enflurane and isoflurane on systemic and pulmonary hemodynamics and metabolic rate was detected. Induction of anesthesia was associated with a decrease in VO2, CI, MAP, and MPAP (P less than 0.001), while SVR and PVR did not change. The decrease in CI paralleled the decrease in VO2, thereby maintaining whole-body O2 supply-demand balance. VO2 decreased most likely because of lessened tissue O2 requirements. When anesthesia was discontinued, all metabolic and hemodynamic variables promptly returned to preanesthetic values. No effect of burn wound excision on pulmonary circulation was detected.

Adult

The reason for cardiac output reduction after aortic cross-clamping.

The hypothesis that a decrease in cardiac output during infrarenal aortic cross-clamping is related to a decrease in oxygen consumption in the perfused tissues (cross-clamp-adapted oxygen consumption) rather than to deterioration of myocardial performance has been tested. Twenty-two patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups of equal number. During aortic cross-clamping, Group 1 patients received nitroglycerin infusion, 1 to 2 micrograms.kg-1.min-1, whereas Group 2 patients did not receive a nitroglycerin infusion. During aortic cross-clamping, cross-clamp-adapted body oxygen consumption decreased equally in both groups by 40 to 42 percent of baseline values, whereas cardiac output decreased by 17 percent in Group 2 but did not change significantly in Group 1. Mixed venous oxygen content increased significantly after induction of anesthesia and prior to aortic cross-clamping in both groups. During cross-clamping, the values of mixed venous oxygen content remained increased in Group 2 and increased further in Group 1. The data support our hypothesis since a decrease in cardiac output was not associated with an increase in filling pressures during aortic cross-clamping, but was instead associated with an increase in mixed venous oxygen content and a decrease in the arteriovenous oxygen content difference. Nitroglycerin infusion was associated with a further increase in mixed venous oxygen content during aortic cross-clamping and a decrease in the arteriovenous oxygen content difference, without a concomitant increase in oxygen utilization.

Aorta, Abdominal