Haemodynamic effects of ATP in dogs during hypoxia-induced pulmonary hypertension.

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03-3.0 micromol/kg/min approximately 0.02-1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose-dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P<0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose-dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.

Management of Jehovah's Witness patients for scoliosis surgery: the use of platelet and plasmapheresis.

Four patients whose religious beliefs prohibited accepting blood during surgery for scoliosis were anesthetized and managed successfully using plateletpheresis and plasmapheresis. Blood losses were replaced with crystalloid and hetastarch solutions. In addition, a moderate hypotensive technique was used to minimize surgical blood loss. Postoperatively, the patients received iron therapy and/or erythropoietin. Three of these patients had an uncomplicated postoperative course, however, the fourth patient had some postoperative bleeding with initial hemodynamic instability. We believe that patients who refuse to receive blood transfusion during surgery because of religious beliefs or health issues can be managed safely using other alternatives and techniques such as plateletpheresis and plasmapheresis, which conserve and minimize blood loss. Each case should be assessed on an individual basis.

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.

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.

Hypothermia minimally decreases nitrous oxide anesthetic requirements.

Over the 38-28 degrees C range, changes in minimum alveolar anesthetic concentration (MAC) parallel changes in lipid solubility of the anesthetics studied. We hypothesized that there would be minimal change in N2OMAC, since N2O lipid solubility is relatively unaltered by temperature changes. We determined N2OMAC in rats using a hyperbaric chamber. In Group N (normothermia, n = 10) rectal temperature was maintained at 37.5 +/- 1 degrees C (mean +/- SD). In Group H (hypothermia, n = 9) temperature was maintained at 29.7 +/- 1.8 degrees C. The hyperbaric chamber was pressurized with N2O and oxygen partial pressure was 0.4 +/- 0.1 atm. Chamber pressure was adjusted approximately 15% up or down, stabilized for approximately 15 min, and the noxious stimulus (electrical current) was applied. This process was continued until two N2O partial pressures were determined which just prevented and just permitted gross, purposeful movement. Nitrous oxide MAC for Group N and Group H were 1.9 +/- 0.2 atm and 1.6 +/- 0.2 atm, respectively, P < 0.01. Temperature and MAC correlated: r = 0.59, P < 0.01. We conclude that hypothermia minimally decreases N2OMAC, which is consistent with the effects of hypothermia on N2O solubility in lipid membranes.

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)

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)

Inhibition of nitric oxide synthesis causes systemic and pulmonary vasoconstriction in isoflurane-anesthetized dogs.

The postulate that the hemodynamic changes produced by isoflurane (1.5%) involve release of nitric oxide (NO) was examined. Fifteen dogs were anesthetized with thiamylal (15 mg/kg) and ventilated with isoflurane and oxygen. Catheters were inserted for measurement of aortic pressure, pulmonary artery pressures, and determination of cardiac output. Left thoracotomy was performed and complete heart block was induced by injection of 37% formaldehyde (0.3 mL) into the atrioventricular node; ventricular rate was fixed at 100 beats/min by external pacing. An apical microtransducer was inserted into the left ventricle (LV) via the apex for measurement of left ventricular pressure (LVP) and its first derivative (dP/dt). Flow probes were mounted on the left circumflex (Cx) and anterior descending (AD) coronary arteries. Measurements were obtained before (control period) and during NO inhibition using IV NG-nitro-L-arginine methyl ester (L-NAME) by a 50 mg/kg bolus plus 1 mg/kg/min. Infusion of L-NAME caused immediate and sustained increases in mean arterial pressure to 145 +/- 3% (P < 0.001), mean pulmonary arterial pressure to 128 +/- 5% (P < 0.001), pulmonary capillary wedge pressure to 144 +/- 8% (P < 0.001), coronary perfusion pressure to 163 +/- 4% (P < 0.001), systemic vascular resistance to 209 +/- 9% (P < 0.001), pulmonary vascular resistance to 142 +/- 12% (P < 0.005), anterior descending flow to 115 +/- 4% (P < 0.005), and circumflex flow to 113 +/- 3% (P < 0.01) of control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutral head position for placement of internal jugular vein catheters.

A new approach to the internal jugular vein is described which keeps the head and neck in the neutral position and uses bony and cartilaginous landmarks for guidelines. Venous puncture is made along an axial line drawn superiorly from the lateral edge of the bony depression caused by the insertion of the sternocleidomastoid muscle on the superior edge of the clavicle. This line, at the level of the cricoid cartilage, lies directly over the internal jugular vein. In 55 patients initially studied, the mean (SEM) number of puncture attempts to locate the vein was 1.4 (0.2) per patient, with an overall success rate of 98%. In 84%, the internal jugular vein was located exactly where predicted, the others were just lateral to the point. The complication rate (all short-term) was 3.6%. Subsequently the internal jugular vein was cannulated successfully using the developed technique in 20 consecutive trauma patients with suspected cervical instability. An average of 1.2 (0.2) (range 1-3) attempts were made per patient to locate the vein and there were no complications. We propose this technique as a safe and reliable method of gaining central venous access in patients with possible cervical spine injury following trauma.

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)

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)

Blood gas and catecholamine levels in capture stressed desert bighorn sheep.

Forty-seven bighorn sheep (Ovis canadensis nelsoni) were captured within a 3-day period in December, 1989 as part of a California Department of Fish and Game effort to repopulate historic ranges in California. They were captured on the Mojave Desert in the Kelso Mountains near Old Dad Peak, San Bernardino County, California. Venous blood gases measured at the site of capture demonstrated a severe metabolic acidosis (base deficit, 23 mEq/liter), with no evidence of respiratory acidosis. There were moderately elevated plasma epinephrine (1.25 ng/ml), norepinephrine (2.60 ng/ml), and dopamine (114 pg/ml) levels. These data appear to reflect animals that have been moderately stressed. These acid-base-catecholamine values differ from values in resting domestic sheep, and are similar to those reported in greyhounds after brief strenuous exercise.

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.

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.

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.

A comparison of midazolam and diazepam for induction of anaesthesia in high-risk patients.

Fifty ASA Class III patients were divided randomly into two equal groups for induction of anaesthesia with diazepam 0.25 mg/kg, or midazolam 0.15 mg/kg. All subjects were premedicated with a narcotic and monitored by ECG, radial arterial catheter and a spirometer for measurement of minute ventilation. The QF interval (time period from the Q wave of the ECG to the foot of the radial artery pulse), mean arterial pressure, heart rate and minute ventilation were recorded before, during and immediately after the induction of anaesthesia. Although mean arterial pressure fell slightly (6%) following midazolam, all other cardiovascular variables were stable in both groups. Minute ventilation was depressed to 70% of control by both drugs and nearly one-half the diazepam patients complained of pain on injection compared with only one midazolam patient. These data suggest that midazolam is a reasonable alternative to diazepam for induction of anaesthesia in the high-risk patient.

The influence of adenosine triphosphate on left ventricular function and blood flow distribution during aortic crossclamping in dogs.

To evaluate the influence of adenosine triphosphate (ATP)-induced vasodilation on myocardial performance and blood flow during aortic crossclamping (XC), ten dogs were instrumented to measure left ventricular (LV) pressure and dimensions. Regional LV function was assessed from the percentage of systolic shortening, whereas the slope of the linear regression of the LV end-systolic pressure-diameter relationship was used as an index of overall contractility. The regional blood flow distribution was measured from sequential injections of radioactive microspheres. Following XC, systemic arterial pressure proximal to the clamp (SAPa), LV end-diastolic pressure (LVEDP), LV end-systolic meridional wall stress (WS), and central venous pressure (CVP) increased significantly, whereas the cardiac index (CI) and heart rate did not change. After 30 minutes of ATP infusion (1 mg/kg/min) SAPa, LVEDP, WS, and CVP returned to control levels, CI increased significantly compared with XC alone, and vascular resistance fell below the control level. ATP produced a threefold increase in myocardial blood flow and shifted the intramural distribution in favor of the endocardial layer. In conclusion, our investigation of the effect of ATP on aortic XC in a canine model showed the drug to produce a smooth, predictable, and rapid reduction in left ventricular preload and afterload. This was accomplished with minimal changes in distal organ perfusion, some improvement in measured cardiac performance, and a large increase in myocardial blood flow.