Cerebral protection with thiopentone during combined carotid endarterectomy and clipping of intracranial aneurysm.

We report a case of carotid endarterectomy and clipping of an ipsilateral internal carotid artery aneurysm in a patient with complete contralateral carotid stenosis. The patient developed an ischaemic electroencephalographic (EEG) tracing on temporary carotid clamping and bypass shunt was contraindicated. We used thiopentone titrated to EEG burst suppression for pharmacological cerebral protection during the subsequent prolonged carotid clamp necessary for carotid endarterectomy. We review the use of thiopentone for this purpose, in particular the evidence for efficacy, mechanism of action and optimal dosage and timing of administration.

The effect of clysed and topical epinephrine on intraoperative catecholamine levels.

BACKGROUND: Epinephrine administration for hemostasis during burn wound excision may produce potential anesthetic risks. Two patient groups were studied to determine the absorption of either topical concentrated epinephrine or exogenously injected dilute epinephrine. METHODS: For the topical group (10 patients, 10 procedures), excision of wounds under tourniquet was performed, followed by epinephrine (1 mg/10 mL) gauze with pressure wrapping. For the clysis group (9 patients, 12 procedures), donor sites were injected with 0.5 mg epinephrine/1,000 mL lactated Ringer's solution before harvest. Nine intraoperative serum samples were collected and frozen during each procedure for epinephrine and norepinephrine assay. RESULTS: Concentrated epinephrine (67 mL) was topically applied to excise 1,362 cm2. Dilute epinephrine (1,350 mL) was clysed to obtain 1,950 cm2 autograft. No significant increases in the serum catecholamines or changes in the cardiovascular profiles occurred. CONCLUSION: The administration of either topical or clysed epinephrine during acute burn excision does not cause any side effects for safe anesthetic management; there were no detectable increased plasma levels of epinephrine or norepinephrine. Epinephrine provides the burn surgeon with two safe methods for controlling intraoperative blood loss.

Effects of hypertonic saline on regional function and blood flow in canine hearts during acute coronary occlusion.

Small-volume resuscitation using hypertonic saline (7.5%) is effective for various types of shock. Recently, hypertonic saline has been proposed for fluid management in patients with impaired cardiovascular function. Whether hypertonic saline is safe in the compromised heart during coronary occlusion is not known. We examined the effects of hypertonic saline at 4 mL.kg-1 on myocardial function and blood flow during acute coronary occlusion. In anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers. Myocardial contractility was assessed using percent of systolic shortenings measured in both normal or ischemic regions. Blood flow distribution was measured using radioactive microspheres. Percent of systolic shortening and blood flow in the normal myocardium, unaltered by coronary occlusion, increased significantly after hypertonic saline from 11.0 +/- 1.1% to 13.7 +/- 1.4% and from 120 +/- 13 mL.min-1.100 g-1 to 169 +/- 13 mL.min-1.100 g-1, respectively. In the ischemic myocardium, occlusion of the left anterior descending coronary artery markedly decreased percent of systolic shortening from 13.0 +/- 1.2% to 9.3 +/- .9% and blood flow from 98 +/- 13 mL.min-1.100 g-1 to 19 +/- 10 mL.min-1.100 g-1. At peak effect of hypertonic saline contractility and blood flow in the ischemic myocardium decreased to 7.4 +/- .8% and 12 +/- 5 mL.min-1.100 g-1, respectively. Five of the nine dogs developed premature ventricular beats during hypertonic saline infusion. However, no significant changes were observed when normal saline was given at equivalent volumes to hypertonic saline in six dogs. Hypertonic saline was associated with significant increases in heart rate (from 116 +/- 3 beats.min-1 to 129 +/- 5 beats.min-1) and cardiac output (from 2.54 +/- .17 L.min-1 to 3.32 +/- .26 L.min-1). Except for an improved perfusion in the skin, hepatic arterial, and coronary beds, blood flow to the muscle, spleen, jejunum, kidney, and brain was not significantly altered by hypertonic saline. Our data demonstrates variant effects of hypertonic saline on either normal or ischemic myocardium. Whereas contractile function and blood flow in the normal myocardium were improved after hypertonic saline infusion, further decreases in blood flow and contractile function in region distal to coronary occlusion could lead to worsening of ischemic injury. These data suggest that hypertonic saline may be deleterious in hearts with impaired contractile function caused by ischemia.

Small-volume resuscitation using hypertonic saline improves organ perfusion in burned rats.

Resuscitation using small volumes (3-5 mL/kg) of 7.5% hypertonic saline (HTS) is effective for hemorrhagic shock. Whether HTS is beneficial for the initial resuscitation of burn injury is not clear. We compared the hemodynamic effects of HTS versus lactated Ringer's solution (LR) and examined organ tissue perfusion during burn resuscitation (R). Full thickness scald burn (35% of total body surface area) was induced in pentobarbital-anesthetized rats. Regional blood flows were measured using radioactive microspheres before and 30 min after burn, and after R with either HTS (4 mL/kg) or LR (at a dose required for equivalent restoration of arterial blood pressure). Data from the HTS-or LR-resuscitated groups were compared to those from a nonresuscitated group (n = 10 in each group). Mean arterial pressure decreased 30% after burn (from 120 +/- 4 to 84 +/- 5 mm Hg, mean +/- SEM) and returned toward baseline (112 +/- 7 mm Hg) at 10 min after R with HTS (4 mL/kg) or LR (22.6 +/- 0.7 mL/kg), but subsequently decreased to 100 +/- 7 mm Hg with HTS and 105 +/- 5 mm Hg with LR at 30 min. In contrast to LR, resuscitation using HTS was associated with tachycardia. Blood flows to the skin and muscle of the normal or burn regions did not change after fluid resuscitation as compared to a nonresuscitated group. Fluid resuscitation transiently increased intestinal perfusion. Similar improvements in blood flow to the spleen were observed with HTS and LR at 10 min after R (from 128 +/- 10 to 156 +/- 15 and from 113 +/- 10 to 145 +/- 26 mL.min-1 x 100 g-1, respectively). However, at 30 min after R, splenic perfusion in the LR group was not different from that in the nonresuscitated group. Blood flows to the brain and kidney increased 39% and 42%, respectively, with HTS. HTS was also associated with pronounced improvements in blood flows to the heart (from 346 +/- 20 to 631 +/- 37 mL.min-1 x 100 g-1), liver (from 36 +/- 2 to 62 +/- 4 mL.min-1 x 100 g-1), and testis (from 29 +/- 2 to 43 +/- 2 mL.min-1 x 100g-1). Resuscitation using HTS was associated with rapid improvement in organ tissue perfusion in anesthetized rats subjected to burn injury. In comparison to LR, greater increases in blood flows to the heart, kidney, liver, and testis were observed with HTS. The results suggest that significant improvement in blood flow distribution can be achieved using HTS at less than one fifth the volume of LR for the initial treatment of burn shock.

The relationship between systolic pressure and stroke volume describes myocardial contractility.

OBJECTIVE: To develop a method of measuring end-systolic elastance from information obtained outside the ventricle and thereby simplify its transduction. DESIGN: Prospective, within-animal comparative analysis. SETTING: University-based laboratory study. PARTICIPANTS: Six mixed-breed dogs. INTERVENTIONS: Instrumentation included minor axis sonomicrometry, ascending aortic flow probe, aortic and ventricular pressure transducers, and constricting cuffs on the vena cavae and aorta. MEASUREMENTS AND MAIN RESULTS: Elastance was determined from the equation PES = EES (VED - VES), where VED - VES is stroke volume and PES is end-systolic arterial pressure. EES was derived from both preload and afterload manipulation. Cardiac performance indices were calculated automatically by computer under conditions of varying load and inotropy. This extraventricular method of elastance calculation was compared by linear regression and analysis of variance to preload recruitable stroke work, traditional EES determination (using ventricular dimension instead of volume), and LVdP/dt at 50 mmHg. EES measured from the aortic sites correlated well with the other contractility indicators (p < 0.003 in all cases) and demonstrated more sensitivity and stability under loading manipulation than traditional EES. A strong relationship between the change in stroke volume and end-systolic ventricular diameter during acute aortic constriction (r = 0.924, p < 0.0001) was observed, and the mean r value for the individual outflow elastance measurements was 0.97 +/- 0.02. CONCLUSIONS: In this study, measurement of EES from the ventricular outflow tract during progressive aortic constriction produced results more consistent and descriptive than EES by traditional techniques and has the potential for obtaining elastance measurements from possibly less invasive techniques.

Potency (minimum alveolar anesthetic concentration) of isoflurane is independent of peripheral anesthetic effects.

The spinal cord is an important site where inhaled anesthetics suppress movement in response to noxious stimuli. Inhaled anesthetics also act in peripheral tissues, although it is unclear whether these actions influence anesthetic requirements. In six isoflurane-anesthetized mongrel dogs, we placed Y cannulas in the lower aorta and vena cava, allowing us to divert blood to, and infuse blood from, a bubble oxygenator/roller pump system or to maintain normal blood flow. This technique permits a greatly diminished isoflurane concentration at the site of the noxious stimulus (tail), while maintaining isoflurane in the remainder of the body. After baseline minimum alveolar anesthetic concentration (MAC1) was determined, venous blood from the lower body was diverted to the bubble oxygenator and reinfused into the lower body via the aortic cannula; MAC2 was determined with isoflurane in the lower body at approximately 0.2%, and MAC3 was determined with isoflurane in the lower body matched to the end-tidal isoflurane. Bypass was terminated, the native circulation established, and MAC4 determined. MAC1, 2, 3, and 4 were (mean +/- SD) 1.3 +/- 0.3%, 1.2 +/- 0.1%, 1.2 +/- 0.2%, and 1.1 +/- 0.2%, respectively (P > 0.05). We conclude that the peripheral effects of isoflurane do not influence the response to a noxious stimulus.

Regional myocardial function during contiguous ischaemia in an anaesthetized canine model: comparison of six methods of measurement.

During acute myocardial ischaemia, the function of the unaffected muscle is the primary determinant of residual cardiac performance. We compared six methods of measuring regional function in the remaining non-ischaemic segment after acute ligation of the left anterior descending (LAD) coronary artery in 16 dogs. Preparation included left ventricular micromanometers, regional sonomicrometer transducers to measure segment length and wall thickness, caval occluders and left atrial catheters for injection of radioactive microspheres to measure regional blood flow. Pulmonary artery, central venous and systemic arterial pressures were measured and regional coronary venous blood was collected for direct myocardial oxygen consumption (VO2) calculations. Under basal high-dose fentanyl-neuromuscular blocker anaesthesia, the LAD was occluded after addition of halothane or isoflurane at 0.5 or 1.5 MAC concentrations. Regional myocardial function of the non-ischaemic segment was assessed by the following computer-derived indices: percent systolic wall thickening (% WT), velocity of shortening (vs), percent systolic shortening (%SS), regional stroke work (RSW), regional preload recruitable stroke work (RPRSW) and regional end-systolic elastance (Ees). No index demonstrated enhanced function in the non-ischaemic segment after LAD ligation and all monitors, except Ees, were sensitive to depression of function represented by a decrease in values after administration of halothane and isoflurane (P < 0.05). Ees values increased with the addition of isoflurane and remained constant with halothane. Circulating concentrations of catecholamines were unchanged after ischaemia, while inhalation agents caused a decrease in the concentrations of adrenaline and dopamine (P < 0.05), but not noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of nitric oxide inhibition on the coronary vasomotor responses to etomidate, propofol, and thiopental in anesthetized dogs.

We examined the hypothesis that the coronary vasomotor responses to etomidate (ETO), propofol (PRO), and sodium thiopental (STP) are mediated through contrasting effects on the resting nitric oxide (NO)-dependent vasodilator tone that opposes adrenergic vasoconstrictor activity in the intact dog. Circumflex flow (CxF) responses to randomized intracoronary microinjections (0.3 mL) of normal saline (NS), alkalinized saline (AS), intralipid (IL), adenosine (ADE, 17 micrograms), acetylcholine (ACh, 1.25 micrograms), ETO (6, 12, 60 micrograms), PRO (30, 60, 300 micrograms), and STP (75, 150, 750 micrograms) were quantified in eight isoflurane-anesthetized dogs with fixed ventricular rates (100 bpm). Injections were repeated during intravenous (IV) infusion (50 mg/kg + 1 mg.kg-1.min-1) of NG-nitro-L-arginine methyl ester (L-NAME). ADE and ACh transiently increased CxF to 305% +/- 20% (P < 0.001) and 310% +/- 29% (P < 0.001) of resting values, respectively. ETO had no effect, whereas PRO (300 micrograms) provoked small transient increases in CxF to 135% +/- 4% (P < 0.05) of control. Responses to STP (750 micrograms) were characterized by momentary decreases to 74% +/- 4% (P < 0.001), followed immediately by increases to 183% +/- 11% (P < 0.001) of resting values; NS AS, and IL had no effect. The momentary decreases with STP (750 micrograms) were significantly augmented during NO inhibition with CxF declining to 49% +/- 7% (P < 0.001) of resting values, whereas the secondary increase was unchanged. With L-NAME, CxF responses to ACh were attenuated to 32% +/- 3% (P < 0.001) of control, whereas responses to ADE, ETO, and PRO were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

A method for preferential delivery of volatile anesthetics to the in situ goat brain.

BACKGROUND: As part of studies aimed at better defining the effects of anesthetics at different anatomic sites, we have developed a model of preferentially delivering inhaled anesthetics to the in situ goat brain, using a bubble oxygenator and roller pump. We tested the hypotheses that (1) this model excludes the cerebral circulation from the body; (2) the concentration of halothane in the oxygenator exhaust correlates with the concentration of halothane in the oxygenator arterial blood. METHODS: After ligation of the occipital arteries in six halothane-anesthetized goats, we used a bubble oxygenator to perfuse the brain preferentially (exclusive of the body) via a carotid artery, draining cranial venous blood back into the oxygenator via the isolated jugular veins. (In goats, the vertebral arteries do not directly contribute to the cerebral circulation, and internal jugular veins and extracranial internal carotid arteries are absent). The extent of isolation was determined with radioactive microspheres injected into the left atrium during the following periods: (1) baseline; (2) during bypass when the blood pressure in the head equalled that in the body; (3) during bypass when the blood pressure in the body exceeded that in the head by approximately 30-35 mmHg; (4) when the bypass roller pump was stopped. We also measured the concentration of halothane in the arterial blood of the bypass unit. In three animals, systemic metocurine was administered during bypass to detect the presence of venous contamination. RESULTS: Baseline cerebral blood flow was 74 +/- 32 ml.100 g-1.min-1 (mean +/- SD). During bypass, cerebral blood flow originating from the systemic circulation was less than 1 ml.100 g-1.min-1, and isolation extended to the caudal medulla during periods 3 and 4, and to the first 1-cm segment of the spinal cord during period 2. The concentration of halothane in the oxygenator exhaust correlated reasonably well with the arterial halothane concentration (r = 0.82, P < 0.001). Systemic arterial metocurine concentrations peaked at 1 min (27 +/- 3.7 micrograms/ml) and decreased to 10.6 +/- 2.3 micrograms/ml at 10 min; head venous metocurine plasma concentrations gradually increased to 3.1 +/- 0.4 micrograms/ml at 10 min. CONCLUSIONS: This technique permits selective perfusion and delivery of inhaled anesthetics to the in situ goat brain, but is not adequate for selective delivery of fixed intravenous anesthetics.

Role of systemic arterial pressure, heart rate, and derived variables in prediction of severity of myocardial ischemia during acute coronary occlusion in anesthetized dogs.

The present study examined the postulate that the quotient of mean systemic arterial pressure and heart rate predicts the severity of myocardial ischemia during occlusion of the left anterior descending coronary artery. Studies were performed in open-chest fentanyl-anesthetized dogs before and during halothane (n = 8) or isoflurane (n = 8) anesthesia. The pressure-rate quotient (PRQ) decreased significantly in both groups during incremental increases in halothane or isoflurane to 68% and 57% of control values at 0.5 MAC and to 41% and 38% at 1.5 MAC for halothane and isoflurane, respectively. Myocardial lactate production was unchanged from the ischemic region, and no correlation between the PRQ and myocardial lactate production was observed. In contrast, heart rate correlated significantly (r = 0.376; P less than 0.05) with lactate production. The product of systolic systemic arterial pressure and heart rate (rate-pressure product) correlated with blood flow (r = 0.493; P less than 0.001) and with oxygen consumption (r = 0.571; P less than 0.001) in the normal myocardium. A weak correlation (r = 0.330; P less than 0.05) of rate-pressure product with myocardial lactate production from the ischemic region was observed. There were no correlations between the PRQ and myocardial lactate production from the ischemic region or indices of blood flow distribution (i.e., inner/outer ratio in the ischemic region or ischemic/normal ratio). The relationship of hemodynamic variables to measurements of regional myocardial metabolism was independent of background anesthetic agent of depth of anesthesia. The current data suggest that heart rate changes are weakly predictive of severity of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary bypass does not alter canine enflurane requirements.

This study determined the effect of cardiopulmonary bypass (CPB) on canine enflurane minimum alveolar concentration (MAC). Fourteen dogs were anesthetized with enflurane in N2O and O2, and after tracheal intubation, the N2O was discontinued. Femoral arterial and pulmonary arterial catheters were placed, and MAC was determined with the tail-clamp method. CPB was initiated via the femoral artery-vein route, with additional venous return obtained from an external jugular vein. Partial CPB was used in the first 10 dogs. In 4 dogs, a membrane oxygenator (group 1) was used, and in the next 6 dogs a bubble oxygenator (group 2) was used. In 4 additional dogs (group 3), using bubble oxygenators, total CPB was achieved by occlusion of the pulmonary artery via a left thoracotomy. The CPB circuit was primed with Ringer's lactate, and circuit blood flows were 70-125 ml.kg-1.min-1, with mean arterial pressures maintained at 50-110 mmHg. MAC was determined again after termination of CPB. In 10 dogs, MAC was also measured during CPB. In 5 dogs MAC was measured after administration of protamine. MAC in all 14 dogs did not change (2.2 +/- 0.3 vs. 2.3 +/- 0.3). MAC remained constant in group 1 (2.4 +/- 0.3 vs. 2.3 +/- 0.4), group 2 (2.2 +/- 0.2 vs. 2.3 +/- 0.3), and group 3 (2.2 +/- 0.1 vs. 2.3 +/- 0.1). Similarly, MAC was unchanged during CPB (2.2 +/- 0.2 vs. 2.2 +/- 0.2) and after protamine (2.3 +/- 0.2 vs. 2.2 +/- 0.3). Temperature was 38.3 +/- 1.2 prebypass and 37.9 +/- 0.9 postbypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of hypotension following rapid infusion of protamine sulfate in anesthetized dogs.

Protamine sulfate (PS), used to neutralize the anticoagulant effect of heparin, is often associated with systemic hypotension. Whether this hypotension is secondary to a depression of myocardial function is not clear. The present study tested the hypothesis that systemic hypotension was accompanied by a depression in myocardial function and examined the possible role of histamine in mediating the cardiovascular response to PS. Seven conditioned dogs were chronically instrumented with pressure and ultrasonic dimension transducers. Studies were conducted under halothane anesthesia 7 to 10 days after instrumentation. Cardiac contractility was assessed using the slope, Ees, of the linear regression of the left ventricular end-systolic pressure-diameter relationship. Intravenous infusion of PS, 5 mg/kg, when given in periods of less than 30 seconds, decreased systemic arterial pressure by 45% (from 101 +/- to 54 +/- 5 mm Hg) without change in heart rate. Cardiac output decreased by 22% from control and the slope Ees decreased by 37% (from 14.5 +/- 1.2 to 8.7 +/- 1.4 mm Hg/mm). Systemic vascular resistance decreased by 34% (from 2581 +/- 121 to 1712 +/- 200 dyne.s.cm-5). The cardiovascular depression caused by PS was transient and could not be reproduced by a repeated dose given within a 60-minute period. Antagonists of histamine (diphenhydramine and cimetidine) could not attenuate the PS-induced cardiovascular depression. This depression was independent of preheparinization and did not occur when PS was infused slowly over a 2-minute period. The data clearly demonstrate negative inotropic and vasodilator effects of PS following rapid administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular function during induced hypotension by fenoldopam or sodium nitroprusside in anesthetized dogs.

Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for induced hypotension because it effectively lowers arterial blood pressure and improves renal perfusion. We examined cardiovascular functions during hypotension induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers for the assessment of LV contractility using the analysis of the pressure-diameter relationship. Blood flow distribution was measured by radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension, fenoldopam and nitroprusside caused similar increases in heart rate (17% +/- 4% vs 19% +/- 10%, respectively) and decreases in systemic vascular resistance (-24% +/- 5% vs -27% +/- 4%). Hypotension induced by fenoldopam was associated with higher LV end-diastolic pressure (4.4 +/- 0.6 vs 2.5 +/- 1.1 mm Hg) and end-systolic meridional wall stress (33.0 +/- 4.3 vs 17.8 +/- 2.1 g/cm2) when compared with nitroprusside. There were no significant changes in cardiac output and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic pressure-diameter relationship, velocity of shortening of the diameter, and percentage of wall thickening of the LV. In contrast to nitroprusside, which decreased renal blood flow from 197 +/- 19 to 163 +/- 15 mL/min, renal blood flow increased during fenoldopam-induced hypotension from 187 +/- 20 to 239 +/- 18 mL/min. The increase in renal perfusion was similar in upper, middle, and lower regions of the kidney; however, it was more in the medulla compared with the cortex (37% +/- 17% vs 25% +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Development of a near anesthetic-free isolated canine hindlimb model. The effects of halothane and atropine sulfate on vascular resistance.

A denervated, isolated canine hindlimb (HL) model was developed to minimize residual anesthetic contamination. To test the preparation, we determined the peripheral arterial vascular effects of atropine sulfate and the effect of the basal anesthetic on arterial resistance. In four dogs that were under halothane and oxygen anesthesia, the HL was prepared to allow either vascular isolation of the limb or continuity with the systemic circulation. During isolation the HL was perfused by roller pump at a preset flow rate through an infant oxygenator. Inspired gas fed to the oxygenator contained either 0%, 1.25%, or 2.5% halothane to determine that anesthetic's effect on HL arterial vascular resistance. No halothane (0%) was used in the oxygenator inflow during the atropine measurements. Vascular resistance was calculated from HL arterial pressure at constant flow. Halothane caused a significant stepwise fall in vascular resistance, with a decrease of 68% at 2.5% inspired concentration (p less than 0.01). Atropine produced a progressive attenuation of resistance that decreased by 18% after the 2.5 mg/kg dose (p less than 0.01). The model proved stable over time and demonstrated an apparent direct, dose-dependent vasodilating effect of both atropine and halothane in the canine HL muscle arterial bed.

Acute hypotension caused by rapid hypertonic saline infusion in anesthetized dogs.

Small volumes (4-6 mL/kg) of 7.5% hypertonic saline solution (HTS) are reported to be effective for resuscitation from circulatory shock. When infused rapidly into either hypovolemic or normovolemic subjects, HTS can cause an immediate and severe hypotension before cardiovascular improvement. In the present study, we examined the hypothesis that the early hypotension produced by HTS was mediated by an acute and transient depression of cardiac contractility. left ventricular pressure and wall motions were measured simultaneously in 10 anesthetized dogs for the assessment of cardiac contractility. Infusion of HTS at 3 mL/kg in 1 min significantly decreased mean arterial blood pressure by 49%, from 95 +/- 4 to 51 +/- 5 mm Hg (P less than 0.05, mean +/- SEM) at 45 s after the onset of infusion. This initial decrease in arterial blood pressure was abrupt and transient (106 +/- 9 s). Concomitantly, cardiac output and coronary blood flow increased significantly from 2.8 +/- 1.0 to 3.9 +/- 1.1 L/min and from 23.7 +/- 5.3 to 49.8 +/- 4.7 mL/min, respectively. Although heart rate remained constant, systolic shortenings of left ventricular diameter and wall thickness increased from 5.6% +/- 0.5% to 7.8% +/- 0.5% and from 13.9% +/- 0.6% to 15.1% +/- 1.2%, respectively, indicating an improvement in cardiac contractility. This was confirmed by subsequent analysis of the left ventricular end-systolic pressure-diameter relationship. Systemic and pulmonary vascular resistance decreased by 60% and 27%, respectively. Despite an initial period of hypotension after rapid infusion of HTS, mean arterial blood pressure, cardiac output, and contractility were all significantly increased at 5 min after HTS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

No evidence for blood flow redistribution with isoflurane or halothane during acute coronary artery occlusion in fentanyl-anesthetized dogs.

The present study examines the postulate that isoflurane, in contrast to halothane, causes redistribution of blood flow away from an ischemic myocardial region through vasodilation of adjacent normally perfused myocardium. The study was performed in open-chest dogs anesthetized with fentanyl; ischemia was induced by occlusion of the left anterior descending coronary artery. At 0.6% alveolar concentration, isoflurane increased transmural blood flow to 125% of control values (P less than 0.05) in the normal region without concomitant changes in blood flow to the ischemic region or in the endocardial/epicardial flow ratio in the ischemic region. The evidence excludes either transmural steal or regional redistribution phenomena. Myocardial blood flow variables returned to control values at 1.8% isoflurane, and no blood flow redistribution effects were evident. In contrast, whereas halothane 0.4% caused no significant effect on myocardial blood flows, an alveolar concentration of 1.2% decreased transmural blood flow to normally perfused left ventricle to 70% of control (P less than 0.05). Regional myocardial oxygen consumption in the normal and ischemic areas decreased at higher alveolar concentrations and was unchanged at the lower concentrations for both agents. Myocardial lactate production from the ischemic region was unchanged with either agent, suggesting that, in terms of metabolic changes, neither agent worsened ischemia during sustained occlusion of the left anterior descending coronary artery. The present data show no evidence for worsening of myocardial ischemia with either isoflurane or halothane. Isoflurane causes a relatively greater increase in perfusion compared to myocardial oxygen consumption of normally perfused myocardium; nevertheless, sufficient coronary vascular reserve remains in the native collateral circulation so that myocardial metabolic supply-and-demand relationships during ischemia are not further compromised.

Cardiac contractility and blood flow distribution following resuscitation with 7.5% hypertonic saline in anesthetized dogs.

We examined the specific effects of 7.5% hypertonic saline (HTS) on myocardial performance and regional blood flow and compared the efficacies of HTS and lactated Ringer's solution (LR) for hypovolemic resuscitation. Studies were performed in anesthetized dogs subjected to rapid hemorrhage to decrease mean arterial pressure by 50% over 60 min. The animals were resuscitated with either HTS (n = 8) at 5 ml/kg or LR (n = 7) at a dose required for equivalent restoration of cardiac output. Cardiac contractility was assessed using the slope Ees of the left ventricular end-systolic pressure-diameter relationship and regional blood flow was measured using radioactive microspheres. At 10 min after resuscitation, mean arterial pressure increased from 45.1 +/- 2.5 to 77.7 +/- 3.2 mmHg with HTS and 50.9 +/- 2.5 to 80.1 +/- 3.2 mmHg with LR. Resuscitation with either fluid caused significant increases in heart rate and similar decreases in vascular resistance. Cardiac contractility (Ees) did not change significantly with LR, whereas with HTS, Ees increased from 14.8 +/- 0.9 during hemorrhage to 19.4 +/- 1.6 as compared with a baseline value of 13.4 +/- 1.5 mmHg/mm. Hemorrhage decreased blood flow to various organs by 50% to 70% of baseline. Except for better improvement in splenic and hepatic perfusion with HTS, similar restoration of blood flow to the heart, muscle, skin, kidney, and jejunum was observed at 10 min after resuscitation with either fluid. In this animal model of rapid and severe hemorrhagic shock, HTS given at approximately one-sixth the volume of LR was equally effective in providing temporary restoration of hemodynamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease in vascular resistance in the isolated canine hindlimb after graded doses of alfentanil, fentanyl, and sufentanil.

Under halothane anesthesia five dogs were prepared with both hindlimbs isolated from the systemic circulation to allow intermittent placement on extracorporeal perfusion at constant flow. One limb of each dog was surgically denervated. In this relatively anesthetic-free preparation, graded equivalent doses of alfentanil, fentanyl, and sufentanil were infused over 30 s, and vascular resistance was measured. Increasing opioid administration caused a progressive diminution in peripheral resistance. By the high dose level, alfentanil (500 micrograms/kg), fentanyl (50 micrograms/kg), and sufentanil (6 micrograms/kg) caused equal and significant decreases of 48%, 48%, and 44% in resistance, respectively. There was no difference among the opioids in effects on resistance at equivalent dosages. Neither pretreatment with naloxone nor denervation changed the response to the narcotics. We conclude that the three synthetic opioids produce vasodilation by direct action on the peripheral vascular smooth muscle.

Hyperbaric oxygen increases survival following carotid ligation in gerbils.

We studied the effects of graded exposure to hyperbaric (1,875 mm Hg) oxygen therapy in an acute stroke model prepared by unilateral carotid artery interruption in gerbils. Pentobarbital alone, superoxide dismutase alone, two periods of hyperbaric oxygen alone, and each agent combined with hyperbaric oxygen were administered to investigate possible mechanisms of protection from cerebral ischemia. Survival rates and neurologic deficit scores over 5 days in all treated groups were compared with those in a control group. Survival rates in the groups subjected to 2 (63.9 +/- 4.0%) and 4 hours (70.1 +/- 5.2%) of hyperbaric oxygen alone were significantly higher than in the control group (53.6 +/- 4.2%). The group treated with pentobarbital alone also demonstrated increased survival (69.8 +/- 7.0%), but the combination of therapeutic regimens offered no apparent additive protection. By 5 days there were no differences in the neurologic deficit scores of the survivors in the groups. The toxic pulmonary effects of hyperbaric oxygen were assessed in a pilot LD50 study. The pressure used caused no mortality during 4 hours of exposure, and the calculated LD50 was 7.26 hours. This investigation demonstrates that graded doses of hyperbaric oxygen given after the insult increase survival in a gerbil model of stroke.

Malignant hyperthermia in humans--standardization of contracture testing protocol.

Malignant hyperthermia (MH) diagnostic biopsy centers across North America have not previously been standardized in regard to protocols and specific muscles. Recent standardization criteria prompted this study of the vastus and rectus abdominis muscles. This study evaluated changes in contracture tension after electrical stimulation of 271 bundles taken from the vastus (n = 16) and rectus abdominus (n = 19) muscle biopsies of normal individuals when exposed to tissue baths in the absence of and in the presence of caffeine (0.5, 1.0, 2.0, 4.0, 8.0, and 32.0 mM) alone, halothane (1% or 3%) alone, or the combination of halothane (1%) plus caffeine (0.25, 0.5, 1.0, 2.0, 4.0, and 32.0). Caffeine threshold concentration was that concentration of caffeine that produced a 7% increase in tension. Caffeine specific concentration (CSC) and halothane caffeine specific concentration (HCSC) were those concentrations of caffeine alone or of halothane plus caffeine that produced a 1 g increase in tension. The concentration of caffeine alone that increased the contracture tension by 7% averaged 6.7 +/- 0.3 mM for vastus, significantly greater than 4.1 +/- 0.2 mM for the rectus muscle biopsies. Caffeine specific concentration was significantly greater for vastus muscle (7.7 +/- 0.7 mM) than it was for rectus muscle (4.9 +/- 0.4 mM). Three percent halothane alone showed contractures in 3/41 vastus (all less than 0.5 g) and 18/54 rectus muscle bundles (8 greater than 0.5 g). Mean HCSC was statistically significantly greater for vastus muscle (1.9 +/- 0.2 mM) than for rectus muscle (1.2 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)