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Biomedical subjects

S E Ricksten

Publications and source records attributed to S E Ricksten.

At least 19 recordsLinked to original sources

Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure.

BACKGROUND: Short-term infusion of atrial natriuretic peptide (ANP) increases renal blood flow (RBF) and glomerular filtration rate (GFR) in patients with acute renal dysfunction. In the present study we evaluated the effects of long-term infusion (>48 h) of ANP on (RBF) and (GFR) in 11 postcardiac surgical patients requiring pharmacological circulatory support and with acute renal impairment. METHODS: Urinary clearance of Cr-EDTA and PAH as well as central hemodynamic measurements were performed for 2-3 consecutive 30-min periods during ANP infusion (50 ng. kg-1. min-1), one hour after abrupt discontinuation of ANP and again immediately after reinstitution of ANP infusion. RESULTS: During ANP infusion, urine flow (UF), GFR, RBF and renal vascular resistance (RVR) were 6.4+/-1.1 ml. min-1, 19.9+/-3.1 ml. min-1, 408+/-108 ml. min-1 and 0.286+/-0.054 mmHg. min. ml-1, respectively. UF, GFR and RBF decreased significantly by 28% (P<0.001), 32% (P<0.01) and 31% (P<0.05), respectively when ANP infusion was discontinued. RVR increased by 93% (P<0.05) while there was no change in filtration fraction. After reinstitution of ANP infusion, all measured renal variables returned to baseline. There was no significant correlation between the number of ANP treatment days and the percentage decrease in GFR (r=0.18) or RBF (r=0.22) during ANP withdrawal. Central hemodynamic variables were not affected by ANP withdrawal. CONCLUSIONS: ANP infusion improves RBF and GFR in patients with acute renal impairment after cardiac surgery. This renal vasodilatory effect is maintained during a long-term infusion and seems to be hemodynamically safe.

Acute Kidney Injury↗

Jejunal mucosal perfusion is well maintained during mild hypothermic cardiopulmonary bypass in humans.

UNLABELLED: In the present study, the effects of mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP), gastric tonometry, splanchnic lactate, and oxygen extraction were studied in low-risk cardiac surgical patients (n = 10), anesthetized and managed according to clinical routine. JMP was assessed by endoluminal laser Doppler flowmetry. Patients were studied during seven 10-min measurement periods before, during, and 1 h after the end of CPB. Splanchnic oxygen extraction increased during hypothermia and particularly during rewarming and warm CPB. JMP increased during hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher 1 h after CPB (42%), compared with pre-CPB control. The gastric-arterial PCO(2) difference was slightly increased (range 0.04-2.26 kPa) during rewarming and warm CPB as well as 1 h after CPB, indicating a mismatch between gastric mucosal oxygen delivery and demand. None of the patients produced lactate during CPB. We conclude that jejunal mucosal perfusion appears well preserved during CPB and moderate (34 degrees C) hypothermia; this finding is in contrast to previous studies showing gastric mucosal hypoperfusion during CPB. IMPLICATIONS: Jejunal mucosal perfusion increases during mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser Doppler flowmetry, gastric tonometry, and measurements of splanchnic lactate extraction could not reveal a local or global splanchnic ischemia during or after CPB. A mismatch between splanchnic oxygen delivery and demand was seen, particularly during rewarming and warm CPB.

Aged↗

The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension.

UNLABELLED: Selective pulmonary vasodilation is an advantageous therapeutic strategy for cardiac surgical patients with increased pulmonary vascular resistance (PVR) and right ventricular failure. We hypothesized that milrinone, an adenosine-3',5'-cyclic monophosphate (cAMP)-selective phosphodiesterase enzyme (PDE) inhibitor may, when nebulized and inhaled, cause selective pulmonary vasodilation and potentiate the vasodilation by inhaled prostacyclin (iPGI(2)). Consequently, we investigated the hemodynamic effects of inhaled milrinone or the combination iPGI(2) + inhaled milrinone in cardiac surgical patients with postoperative mean pulmonary arterial pressure (MPAP) >25 mm Hg and PVR >200 dynes. s(-1). cm(-5). During mechanical ventilation and using a conventional nebulizing system, 9 patients inhaled incremental concentrations of milrinone (0.25, 0.5 and 1 mg/mL) in subsequent 10-min periods (Study Part 1). In the same manner, 11 patients received iPGI(2) (10 microg/mL) followed by the combination of iPGI(2) (10 microg/mL) and inhaled milrinone (1 mg/mL) (Study Part 2). Inhaled milrinone reduced PVR with a maximal effect (-20%, P < 0.001) at the largest concentration. As compared with iPGI(2) alone, iPGI(2) + inhaled milrinone caused a further and prolonged reduction of PVR (-8%, P < 0.05) and increased stroke volume (+5%, P < 0.05). Systemic vascular resistance or mean arterial pressure was not affected by inhalation of either drug(s). The authors conclude that inhalation of the cAMP-selective PDE-inhibitor milrinone selectively dilates the pulmonary vasculature without systemic effects in cardiac surgical patients with pulmonary hypertension. Furthermore, inhaled milrinone appears to potentiate and prolong the pulmonary selective vasodilatory effect of iPGI(2). Inhaled milrinone alone or combined with iPGI(2) may be an important therapeutic option in the treatment of patients with pulmonary hypertension and right ventricular failure. IMPLICATIONS: Pulmonary hypertension may cause or aggravate right heart failure. IV vasodilators reduce systemic blood pressure and might thereby further impair coronary perfusion and right heart performance. In the present study of cardiac surgical patients with pulmonary hypertension, selective pulmonary vasodilation without systemic effects was induced by nebulized, inhaled vasodilators.

Administration, Inhalation↗

Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass.

OBJECTIVE: To study the effects of 6 h inhalation of aerosolized prostacyclin (PGI2) on platelet function. DESIGN: In a prospective, double-blind, randomized study, 28 patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CPB), received either 0.9% sodium chloride (n = 8), PGI2 5 microg x ml(-1) (n = 10) or PGI2 10 microg x ml(-1) (n = 10) as an aerosol for 6 h postoperatively. SETTING: Cardiothoracic intensive care unit at a university hospital. INTERVENTIONS: All patients were studied immediately after surgery during mechanical ventilation and sedation. The PGI2 solutions or saline were administered with a jet nebulizer. MEASUREMENTS AND RESULTS: Bleeding time and chest tube drainage were measured. Blood samples for platelet aggregation, thrombelastography (TEG) and analysis of coagulation parameters and the stable prostacyclin metabolite 6-keto-PGF1alpha were obtained immediately before inhalation and after 2, 4 and 6 h of inhalation. After 6 h of PGI2 inhalation, regardless of administered dose, there was a lower rate of platelet aggregation and a lower maximal increase in light transmission in response to adenosine diphosphate (ADP) than in the control group. The TEG variable reaction time (R) was prolonged after 4 and 6 h of inhalation in the PGI2 group receiving 10 microg x ml(-1). There were no differences between groups with respect to bleeding time and chest tube drainage or any of the other variables examined. CONCLUSION: Inhalation of PGI2 for 6 h in patients after cardiac surgery is associated with impaired platelet aggregation detected by in vitro techniques, with no in vivo signs of platelet dysfunction.

Administration, Inhalation↗

Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgery.

BACKGROUND: The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). METHODS: The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. RESULTS: At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (-19%), SVR (-27%) and PVR (-15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l x min(-1) x kg(-1), the volume of distribution at steady state was 0.08 l x kg(-1) and the initial and terminal half-lives were <1 min and 4 min, respectively. CONCLUSIONS: Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG.

Antihypertensive Agents↗

Cerebral dysfunction after cardiac surgery--are we moving forward?

This review focuses on the effects of cardiac surgery and cardiopulmonary bypass on the brain, with special emphasis on the results of recently conducted studies. The incidence of postoperative neurological and neuropsychological deficits and risk factors for cerebral injury are reviewed. The relationships between cerebral embolic load, release of biochemical markers of brain injury and cognitive dysfunction after cardiac surgery are also reviewed. Finally, recently gained information on the management of cardiopulmonary bypass is discussed, along with the results of recent pharmacological neuroprotective trials in patients undergoing cardiac surgery.

Journal Article↗

Differential effects of dopamine, dopexamine, and dobutamine on jejunal mucosal perfusion early after cardiac surgery.

OBJECTIVE: To evaluate the potential differential effects of dopamine, dopexamine, and dobutamine on jejunal mucosal perfusion, assessed by endoluminal laser Doppler flowmetry in uncomplicated postcardiac surgical patients. DESIGN: A prospective, blinded, randomized, crossover study. SETTING: A cardiothoracic intensive care unit in a tertiary care center. PATIENTS: A total of ten postoperative cardiac surgical patients were studied. INTERVENTIONS: Each patient received sequentially, randomly, and in a blinded fashion 2.7+/-0.2 microg x kg(-1) x min(-1) dopamine, 0.7+/-0.1 microg x kg(-1) x min(-1) dopexamine, and 2.7+/-0.1 microg x kg(-1) x min(-1) dobutamine. Each inotropic agent was titrated to increase cardiac output by 25% from baseline. Data on jejunal mucosal perfusion, splanchnic lactate, and oxygen extraction were obtained during a 5-min control period and a 5-min drug infusion period after the target cardiac output was reached. The procedure was sequentially repeated for each agent, and there was a 20- to 30-min washout period between each agent. MEASUREMENTS AND MAIN RESULTS: Dopamine, dopexamine, and dobutamine increased jejunal mucosal perfusion by 27% (p < .01), 20% (p < .001), and 7% (p < .001), respectively. The increase in jejunal mucosal perfusion by dopamine and dopexamine were significantly more pronounced compared with dobutamine (p < .05 and p < .01, respectively), whereas there was no difference between dopamine and dopexamine. Splanchnic oxygen extraction decreased to the same extent with all three drugs. Splanchnic lactate extraction did not change for any of the drugs. The effects on central hemodynamics were similar for the three inotropic agents. CONCLUSIONS: Endoluminal laser Doppler flowmetry is a new tool for the detection of perfusion changes at the local intestinal mucosal level. Dopamine, dopexamine, and dobutamine have differential effects on jejunal mucosal perfusion probably because of their different receptor stimulating properties. These findings may be of clinical importance when the therapeutic goal is to improve gut mucosal perfusion.

Adult↗

Jejunal and gastric mucosal perfusion versus splanchnic blood flow and metabolism: an observational study on postcardiac surgical patients.

OBJECTIVES: To evaluate the association between changes in total splanchnic and mucosal perfusion, assessed either by gastric tonometry or jejunal laser Doppler flowmetry in postcardiac surgical patients. DESIGN: A prospective, observational study. SETTINGS: A general intensive care unit in a tertiary care center. PATIENTS: Twelve, postoperative cardiac surgery patients were studied. INTERVENTIONS: Patients were treated according to clinical routine. Total splanchnic blood flow (indocyanine green extraction), jejunal mucosal perfusion (laser Doppler flowmetry), gastric mucosal-arterial PCO2 gradients, and splanchnic lactate uptake were studied during four 30-min measurements periods, each separated by a period of 1 hr. MEASUREMENTS AND MAIN RESULTS: There was no consistent association between either total splanchnic and local mucosal perfusion or between gastric and jejunal perfusion as assessed by two different techniques. The PCO2 gradient increased from 0.73+/-0.21 kPa to 1.15+/-0.30 kPa (p < .05), and splanchnic oxygen extraction increased from 40%+/-9% to 49%+/-14% (p < .01). CONCLUSIONS: In this observational study on postcardiac surgical patients, local mucosal perfusion did not reflect total splanchnic blood flow and vice versa. Either changes in gastric and jejunal mucosal perfusion were different or increasing tissue metabolism was responsible for the observed lack of association between tonometry, laser Doppler flowmetry, and total splanchnic blood flow. Increasing mucosal arterial PCO2 gradient and splanchnic oxygen extraction may reflect a mismatch between splanchnic perfusion and metabolic demands.

Adult↗

Perioperative blood pressure control: a prospective survey of patient management in cardiac surgery.

OBJECTIVE: To conduct a survey of current cardiac anesthetic practice in Europe and the United States, as a first step toward establishing guidelines for the management of perioperative hypertension. DESIGN: Prospective, multicenter study. SETTING: University hospitals. PARTICIPANTS: Unselected patients (n = 1,930) requiring cardiac surgery. INTERVENTIONS: Data extending from the preoperative evaluation to 120 hours or more after surgery were collected from all patients. MEASUREMENTS AND MAIN RESULTS: Only the data from patients undergoing coronary artery bypass surgery, valve surgery, or combined procedures were analyzed, leaving a final total of 1,660 patients from the original 1,930. Of these, 88% were treated at least once perioperatively to lower arterial blood pressure. Deepening of anesthesia was the most commonly used antihypertensive measure (68%), regardless of the ongoing anesthetic regimen, and was usually combined with vasodilator therapy, most frequently nitroglycerin (53%) or sodium nitroprusside (28%). Reported perioperative mean arterial pressure (MAP) was 15 to 20 mmHg lower than MAP before anesthesia induction, regardless of the use of antihypertensive therapy. The MAP at which antihypertensive treatment was initiated varied markedly among the various phases of surgery and showed no clear correlation with preoperative MAP. CONCLUSIONS: The results of this survey show that current anesthetic practice tries to prevent perioperative hypertension wherever possible during cardiac surgery. Blood pressure measurements taken before surgery have little influence on the development of hypertension intraoperatively, and the main determinants of perioperative blood pressure control and the need for therapeutic intervention are factors arising from the surgical procedure itself, such as aortic cross-clamping and activation of adrenergic mechanisms.

Blood Pressure↗

The use of continuous positive airway pressure by face mask and thoracic epidural analgesia after lung transplantation. Gothenburg Lung Transplant Group.

OBJECTIVE: To evaluate the clinical use of continuous positive airway pressure (CPAP) and thoracic epidural analgesia (TEA) after lung transplantation (LTx). DESIGN: Retrospective case series. SETTING: Cardiothoracic intensive care unit (ICU) at a university hospital. PARTICIPANTS: All heart-lung, bilateral, and single-lung transplant recipients between 1990 and 1996 at this institution (n = 102). INTERVENTIONS: Postoperative pain was controlled by a thoracic epidural infusion of bupivacaine, 1 mg/mL, and sufentanil, 1 microg/mL. After extubation, CPAP, 5 to 10 cm H2O by face mask, was used to prevent reperfusion edema. MEASUREMENTS AND MAIN RESULTS: In 99 patients, the length of ventilation (LOV) was a median of 4.3 hours (range, 1.0 to 312.0 hours). The median LOV was 8.0 hours (range, 1.5 to 41.0 hours) in the heart-lung recipients, 4.5 hours (range, 2.0 to 47.0 hours) in the bilateral-lung recipients, and 3.5 hours (range, 1.0 to 312.0 hours) in the single-lung recipients. Three transplant recipients, all with primary pulmonary hypertension, were prematurely extubated and reintubated because of pulmonary edema. Twelve hours after extubation, the median oxygenation index (PaO2/F(I)O2, PaO2 in kilopascal units) was greater than 35. The median ICU length of stay for all transplant recipients was 4 days (range, 2 to 270 days). CONCLUSION: The postoperative use of CPAP and TEA is associated with early and safe tracheal extubation after LTx and may shorten ICU stay.

Adolescent↗

Atrial natriuretic peptide attenuates pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease.

UNLABELLED: Atrial natriuretic peptide (ANP) exerts a dilatory effect on coronary arteries in humans. We investigated the effects of ANP on pacing-induced myocardial ischemia during enflurane anesthesia in patients with coronary artery disease (CAD). In 20 patients with CAD, myocardial ischemia was induced by atrial pacing before and after an i.v. infusion of ANP (50 mg x kg(-1) min(-1), n = 10) or placebo (n = 10). We studied the effects of ANP or placebo on pacing-induced changes in central hemodynamics, myocardial blood flow and regional myocardial indices of lactate uptake (RMLU), and oxygen consumption (RMVO2) and extraction (RMO2E). ST-segment depression was less pronounced during pacing with ANP compared with control pacing (-0.09 +/- 0.01 vs -0.24 +/- 0.02 mV; P < 0.001). RMLU decreased to -11.1 micromol/min during control pacing compared with -0.7 micromol/min during pacing with ANP (P < 0.01). ANP did not affect pacing-induced changes in RMVO2, RMO2E, or the rate pressure product. Placebo did not affect pacing-induced changes in ST-segment depression or RMLU. In conclusion, ANP attenuates ischemic ST-segment depression and lactate release during pacing-induced myocardial ischemia in patients with CAD. The antiischemic effect of ANP was not accompanied by any improvement in the regional myocardial oxygen supply/demand relationship. IMPLICATIONS: We evaluated the effects of i.v. atrial natriuretic peptide (50 ng x kg(-1) x min(-1)) on pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. In contrast to placebo, atrial natriuretic peptide attenuated ST-segment depression and myocardial lactate production and improved left ventricular function during pacing-induced ischemia.

Adult↗

High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower extremities.

BACKGROUND: Sympathetic nerve activity was recorded in the leg during high thoracic epidural anesthesia with a segmental sensory blockade of the upper thoracic dermatomes to test the hypothesis that the sympathetic blockade accompanying thoracic epidural anesthesia includes caudal parts of the sympathetic nervous system. METHODS: Experiments were performed on 10 patients scheduled for thoracotomy. An epidural catheter was inserted at the T3-T4 or T4-T5 interspace. In the main protocol (seven patients), blood pressure, heart rate, and skin temperature (big toe, thumb) were continuously monitored, and multiunit postganglionic sympathetic nerve activity was recorded with a tungsten microelectrode in a muscle-innervating fascicle of the peroneal nerve. After baseline data collection, muscle sympathetic nerve activity was recorded for an additional 45-min period after epidural injection of 4-6 ml bupivacaine, 5 mg/ml. In an additional three patients, the effects of thoracic epidural anesthesia on skin-innervating sympathetic nerve activity were qualitatively assessed. RESULTS: Activation of thoracic epidural anesthesia caused no significant changes in peroneal muscle sympathetic nerve activity (n = 7), blood pressure, or heart rate. Skin temperature increased significantly in the hand 15 min after activation of the blockade, from 32.7 +/- 2.4 degrees C to 34.4 +/- 1.5 degrees C (mean +/- SD), whereas no changes were observed in foot temperature. The sensory blockade extended from T1 (C4-T2) to T8 (T6-T11). CONCLUSIONS: A high thoracic epidural anesthesia with adequate sensory blockade of upper thoracic dermatomes may be achieved without blockade of caudal parts of the sympathetic nervous system. This finding differs from that of earlier studies that used indirect methods to evaluate changes in sympathetic nerve activity.

Anesthesia, Epidural↗

Baroreceptor-mediated reduction of jejunal mucosal perfusion, evaluated with endoluminal laser Doppler flowmetry in conscious humans.

Reduction of central blood volume elicits a peripheral vasoconstrictor reflex in various tissues including skin, skeletal muscle and the hepatomesenteric region. The aim of the present study was to investigate whether this reaction includes a decreased perfusion of the jejunal mucosa in man. Laser Doppler flowmetry (LDF) was used to monitor jejunal mucosal and skin perfusion simultaneously in eleven healthy volunteers. LDF recordings were performed during quiescent (phase 1) periods of the migrating motor complex. Seven subjects demonstrated cycling changes of jejunal mucosal perfusion (vasomotion). The average minimum jejunal flux value was 72 +/- 6 perfusion units. The average intraindividual coefficient of variation was 18 +/- 2%. Lower body negative pressure (LBNP) was used to elicit controlled reductions of central blood volume. LBNP of 10 mm Hg induced a 12 +/- 4% (P < 0.05) decrease in jejunal perfusion and a 43 +/- 11 (P < 0.001) decrease in cutaneous perfusion. Corresponding responses to LBNP of 20 mm Hg were 17 +/- 5% (P < 0.01) and 37 +/- 10% (P < 0.01) reductions in jejunal mucosal and skin perfusion, respectively. Cardiac index was significantly reduced by the LBNP procedure, whereas heart rate remained unchanged and blood pressure changes were minor and inconsistent. These findings indicate that the reflex vasoconstriction induced by mild central hypovolemia includes a significant reduction of jejunal mucosal perfusion in supine resting humans. This reflex may provide one mechanism for the intestinal ischemia often occurring in critically ill patients.

Adult↗

The effects of propofol on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass.

UNLABELLED: We investigated the effects of burst-suppression doses of propofol on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and dynamic autoregulation in 20 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with stable hypothermia (32 degrees C) in fentanyl-anesthetized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Dynamic autoregulation was tested by stepwise changes in mean arterial pressure (MAP) within a range of 40-80 mm Hg by sodium nitroprusside and phenylephrine before (control) and during propofol infusion, with a stable plasma concentration (approximately 9 microg/mL). Propofol induced a 35% decrease in CBFV (P < 0.0001) and a 10% decrease in COE (P < 0.05) compared with control. The slopes of the curves relating CBFV and COE to cerebral perfusion pressure (CPP = MAP - JVP) were less pronounced with propofol (P < 0.01 and P < 0.05, respectively). We conclude that propofol decreases CBFV and improves dynamic autoregulation during moderate hypothermic CPB. Furthermore, during propofol infusion, cerebral blood flow was in excess relative to oxygen demand, as indicated by the decrease in COE. IMPLICATIONS: In this study, we evaluated the effects of propofol on continuously measured cerebral blood flow velocity (CBFV) and cerebral oxygen extraction as a function of perfusion pressure. Propofol induced 35% and 10% decreases in CBFV and cerebral oxygen extraction, respectively. The slope of the curve relating cerebral perfusion pressure to CBFV decreased with propofol.

Aged↗

Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance.

STUDY OBJECTIVE: Elevated pulmonary vascular resistance is a risk factor in heart transplantation and reversibility of high pulmonary vascular resistance is evaluated preoperatively in potential recipients using i.v. vasodilators or inhaled nitric oxide. Prostacyclin is a potent vasodilator, which when inhaled, has selective pulmonary vasodilatory properties. The aim of this study was to compare the central hemodynamic effects of inhaled prostacyclin with those of inhaled nitric oxide in heart transplant candidates. DESIGN: A pharmacodynamic comparative study. SETTING: Cardiothoracic ICU or laboratory for diagnostic heart catheterization at a university hospital. PATIENTS: Ten heart transplant candidates with elevated pulmonary vascular resistance (>200 dynes x s x cm(-5) and/or a transpulmonary pressure gradient > 10 mm Hg) were included in the study. INTERVENTIONS: Nitric oxide (40 ppm) and aerosolized prostacyclin (10 microg/mL) were administered by inhalation in two subsequent 10-min periods. Hemodynamic measurements preceded and followed inhalation of each agent. MEASUREMENTS AND RESULTS: Both inhaled nitric oxide and inhaled prostacyclin reduced mean pulmonary artery pressure (-7% vs -7%), pulmonary vascular resistance (-43% vs -49%), and the transpulmonary gradient (-44% vs -38%). With inhaled prostacyclin, an 11% increase in cardiac output was observed. Other hemodynamic variables, including the systemic BP, remained unaffected by each of the agents. CONCLUSIONS: Inhaled prostacyclin induces a selective pulmonary vasodilation that is comparable to the effect of inhaled nitric oxide. Major advantages with inhaled prostacyclin are its lack of toxic reactions and easy administration as compared with the potentially toxic nitric oxide requiring more complicated delivery systems.

Administration, Inhalation↗

Anti-ischemic and anti-anginal effects of thoracic epidural anesthesia versus those of conventional medical therapy in the treatment of severe refractory unstable angina pectoris.

BACKGROUND: Cardiac sympathetic blockade by thoracic epidural anesthesia (TEA) dilates stenotic coronary arteries and has been used to control pain in patients with unstable angina. The aim of the present study was to evaluate the potential anti-ischemic effects of cardiac sympathetic blockade by TEA in severe, refractory, unstable angina. METHODS AND RESULTS: Forty patients with unstable angina refractory to standard anti-anginal therapy were randomized to receive either continuous epidural infusion of bupivacaine (TEA, Th1 to Th5) or to standard anti-anginal therapy including beta-blockers, calcium antagonists, aspirin, heparin, and nitroglycerin infusion (control group). The primary end points were number of anginal attacks and severity of myocardial ischemia assessed by 48-hour ambulatory Holter monitoring. The incidence of myocardial ischemia was lower in the TEA group (22% versus 61%; P<.05). The number of ischemic episodes per patient was 1.0+/-0.6 in the TEA group and 3.6+/-0.9 in the control group (P<.05). The episode duration per patient was 4.1+/-2.5 minutes and 19.7+/-6.2 minutes in the TEA and the control groups, respectively (P<.05). The mean area-under-the-ST-time-curve was 6.8+/-4.3 and 32.2+/-14.3 (mm-min) in the TEA and the control groups, respectively (P<.05). Fifteen anginal attacks were recorded in the control group and one attack in the TEA group (0.83+/-0.21 versus 0.06+/-0.06/patient, respectively, P<.01). CONCLUSIONS: The anti-ischemic and anti-anginal effects of continuous TEA are superior to those of conventional therapy in the treatment of refractory unstable angina.

Aged↗