Nguyen D. Kien

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 < 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. The results show that acute hypotension caused by rapid infusion of HTS was not mediated by cardiac depression but by a decrease in total peripheral resistance.

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%). Both fenoldopam and nitroprusside decreased splenic blood flow, but neither altered flow to the brain, skin, or myocardium. Muscle and hepatic arterial blood flow were significantly less with fenoldopam than with nitroprusside. Fenoldopam was associated with significantly larger increases in plasma renin activity compared with nitroprusside. The results of this study show an increase in renal blood flow during fenoldopam infusion that may be of advantage particularly when renal hypoperfusion should be avoided.

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 μg/kg), fentanyl (50 μg/kg), and sufentanil (6 μg/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.

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 approximate equals 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. (Anesth Analg 1995;81:69-72)

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 halo-thane-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 μg/ml) and decreased to 10.6 ± 2.3 μg/ml at 10 min; head venous metocurine plasma concentrations gradually increased to 3.1 ± 0.4 μg/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.

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 Ringers 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 centered dot min-1 centered dot 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 centered dot min-1 centered dot 100 g-1), liver (from 36 +/- 2 to 62 +/- 4 mL centered dot min-1 centered dot 100 g-1), and testis (from 29 +/- 2 to 43 +/- 2 mL centered dot min-1 centered dot 100 g-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. (Anesth Analg 1996;83:782-8)

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.

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.

Hemodynamic responses to alfentanil in halothane-anesthetized dogs.

Alfentanil is an opioid that has been used both as a sole anesthetic and in conjunction with other inhalation anesthetics. However, its effects on myocardial performance and regional blood flow are not clearly known. Using sonomicrometry and radioactive microsphere techniques, we examined the hemodynamic responses to alfentanil when given as a loading dose (45 μg/kg) followed by continuous infusion (3 μg·kg−1·min−1) in dogs anesthetized with halothane. Similar plasma levels of alfentanil were observed after the loading and infusion doses, and both techniques of administration produced a significant reduction in arterial pressure without change in global or regional function of the left ventricle. Although cardiac output and left ventricular end-diastolic pressure remained unchanged, heart rate and systemic vascular resistance decreased significantly after the loading dose and recovered slightly when alfentanil was infused continuously. Despite the systemic hypotension, alfentanil did not alter perfusion to the heart, brain, muscle, and skin; however, blood flow to the renal cortex and the arterial supply to the liver decreased by 25 and 60%, respectively. Reduction in blood flow to the kidneys and the liver suggests that alfentanil should be used with caution when normal function of these organs is in question.