Treatment of acute stroke with hyperbaric oxygen: time window for efficacy.

We conducted a retrospective statistical analysis of the Heyman, Saltzman, Whalen 1966 study of 22 stroke patients treated with hyperbaric oxygen (HBO2)--13 of them one to five hours post-stroke. We examined patients who received HBO2 treatment within seven hours post-stroke. An exploratory logistic regression analysis examining the influence of time post-stroke, time in chamber and dose of HBO2, range 2.02 atmospheres absolute (ATA) to 3.04 ATA, was conducted. Only time post-stroke was a significant influence for recovery, with each passing hour decreasing the chance of at least partial transient recovery by 62% - odds ratio: 0.38 (95% CI: 0.15 -0.95), p = 0.039. In the one- to five-hour group of 13 patients, nine (41% of 22) had recovery or recovery with relapse. This represented 69% (+/- 25% SE) of this time frame. Only two of the nine had permanent recovery. Past six hours poststroke, only one patient (11% +/- 21% SE) had partial recovery with relapse. The other eight past six hours had no recovery at all. The first three hours post-stroke HBO2 administration has the most promise for efficacy and improvement of rtPA therapy. HBO2 may also prove to be a useful challenge pre-rtPA administration to assess the risk-benefit ratio for giving rtPA.

Tile water quality following liquid swine manure application into standing corn.

The quality of water draining fields fertilized with liquid swine (Sus scrofa) manure (LSM) sidedressed into standing corn (Zea mays L.) at rates ranging from 0 to 94 m(3) ha(-1), either topdressed (TD) onto the surface, or injected (INJ) into the soil once annually for each of three consecutive years was evaluated. Liquid swine manure application rate was a critical driver of preferential flow of LSM to tile as detected by turbidity, concentrations of NH(4)(+)-N, dissolved reactive phosphorus (DRP), and the presence of enteric bacteria (Escherichia coli). Contaminant movement to drains occurred immediately after 75 and 94 m(3) LSM ha(-1) were injected (e.g., 2.5 mg DRP L(-1), 3-yr average). With injection of 56 m(3) ha(-1) or less, drainage water was not turbid and concentrations of NH(4)(+)-N, DRP, and enteric bacteria were dramatically lower than with the higher rates, even when tiles flowed freely during manure application. Application method also affected tile water quality. With TD applications (37 and 56 m(3) ha(-1)), nutrients and bacteria did not move to tiles at the time of application, but with rains that fell within 3 d after application, concentrations increased (e.g., 0.1 mg DRP L(-1)), although less than with INJ. Overall, sidedress injection rates that supplied adequate crop nutrients did not compromise drainage water quality.

Preservation of myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest with 2, 3-butanedione monoxime.

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.

Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease.

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.

Coronary revascularization in patients with bilateral internal carotid occlusions.

Coronary revascularization that is neurologically uneventful in patients with bilateral totally occluded internal carotid arteries has not been previously reported. We performed saphenous vein coronary artery bypass grafting on three such patients and observed them for 6 to 23 months. Preoperatively two of our patients had chronic stable symptoms of cerebrovascular insufficiency, and one had received cerebral revascularization via a superficial temporal-to-middle cerebral artery bypass. Controversy exists regarding proper cerebral protective maneuvers during coronary revascularization for patients with advanced cerebrovascular disease. Cerebral protection for our patients during cardiopulmonary bypass included hypothermia and high perfusion flows and pressures. Two patients also received prophylactic sodium thiopental. None of these three patients had a stroke perioperatively or during the follow-up period. We believe that these case histories strongly suggest that the functional state of the cerebral collateral circulation, as judged by preoperative neurological symptoms, predicts neurological outcome after coronary revascularization better than the specific occlusive anatomy of the extracranial carotid arteries.

Direct effects of oxygenated crystalloid or blood cardioplegia on isolated myocyte contractile function.

UNLABELLED: The majority of myocardial protective techniques performed in the United States incorporate hypothermic, hyperkalemic blood or crystalloid cardioplegia. Oxygenated blood cardioplegia has not been compared with oxygenated crystalloid cardioplegia in an isolated myocyte model of hypothermic, hyperkalemic cardioplegic arrest in which direct measurements of contractile function and myocyte swelling can be made. Accordingly, isolated myocyte contractile function and myocyte profile surface area were examined after hypothermic arrest with oxygenated crystalloid or blood cardioplegia. METHODS: Isolated left ventricular pig myocytes were randomly assigned to undergo cardioplegic arrest for 2 hours at 4 degrees C. Either oxygenated crystalloid or blood cardioplegia was used. After 2 hours, myocytes were reperfused with standard cell medium at 37 degrees C and contractile function was examined. A control group of myocytes was maintained in cell medium at 37 degrees C for 2 hours. Myocyte velocity of shortening (micrometers per second) was examined at baseline and after beta-adrenergic stimulation (isoproterenol, 25 nmol/L). Velocity of shortening declined equally from baseline control values (65 +/- 2 micron n/sec) in the groups subjected to oxygenated crystalloid cardioplegia and blood cardioplegia (37 +/- 2 micron n/sec and 42 +/- 1 micron n/sec, respectively; p < 0.05). RESULTS: Although beta-adrenergic stimulation caused a significant increase in velocity of shortening in all myocyte groups, the increase was less pronounced in myocytes subjected to crystalloid cardioplegia (157 +/- 6 micron n/sec) and blood cardioplegia (159 +/- 6 micron n/sec) than in normothermic control myocytes (205 +/- microm/sec; p < 0.05). Myocyte profile surface area, an index of cell volume, was measured in all myocyte groups. Myocyte surface area increased equally after cardioplegic arrest and rewarming in both cardioplegia groups (crystalloid 4119 +/- 53 micron2; blood 3924 +/- 48 micron2); surface areas in both cardioplegia groups were significantly greater than in the normothermic control group (3158 +/- 39 micron2, p < 0.05). CONCLUSION: Equivalent effects of oxygenated crystalloid and blood cardioplegia were observed with respect to myocyte contractile function, inotropic responsiveness, and intracellular volume regulatory processes.

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man.

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.

Use of esophageal or precordial stethoscopes by anesthesia providers: are we listening to our patients?

STUDY OBJECTIVE: To ascertain current anesthesia utilization of esophageal and precordial stethoscopes in U.S. anesthesia training programs. DESIGN: Prospective, single-blind, incidence study. SETTING: Operating rooms of three tertiary care hospitals with major academic anesthesiology departments. SUBJECTS: Anesthesia faculty [MD and certified registered nurse-anesthetist (CRNA) staff] and anesthesia trainees (anesthesiology residents and student nurse-anesthetists). INTERVENTIONS: observe and record the placement (stethoscope device appropriately positioned) and utilization (stethoscope in place and connected to the ear piece of the anesthesia provider) of the esophageal or precordial stethoscope during general, regional, and monitored anesthesia care. MEASUREMENTS AND MAIN RESULTS: During 520 anesthetics, an esophageal stethoscope was inserted in 68% of subjects, a precordial stethoscope was positioned in 16%, and an anesthetic stethoscope was absent in 16% of cases. Utilization (stethoscope connected to earpiece) ranged from a low of 11% of cases to a high of 45%, depending on the institution. Overall, providers were listening via an anesthetic stethoscope in only 28% of anesthetics. CONCLUSIONS: Our data suggest infrequent utilization of esophageal and precordial stethoscopes in anesthesia training institutions. Thus, current anesthesia training may be fostering an environment where providers overlook a valuable minimally invasive, and cost-effective continuous monitor of patients' dynamic vital organ function.

Clinical pearls in the anaesthetic management of elderly patients.

Recently published information is changing the approach of anaesthetists to pulmonary aspiration prophylaxis, drug dosing, hypertension during general anaesthesia, hypotension during spinal and epidural anaesthesia, intraoperative hypothermia, and postoperative ileus in elderly patients. Routine aspiration prophylaxis is no longer recommended. Lower drug doses are required to achieve the same endpoints in the elderly as in younger patients. Greater use of antihypertensive drugs rather than additional doses of anaesthetic agents is recommended during general anaesthesia to avoid myocardial depression or prolonged emergence. Routine preoperative volume loading prior to spinal and epidural anaesthesia is being questioned. Tolerance of mean arterial pressures of 65 mmHg during spinal and epidural anaesthesia is encouraged even in patients with hypertension. The adverse effects of inadvertent intraoperative hypothermia are discussed, including the conversion of vecuronium from an intermediate to a long-acting neuromuscular blocking agent. Spinal or epidural local anaesthetics with or without spinal or epidural opioids and ketorolac are associated with less postoperative ileus than postoperative analgesia based on opioids administered intravenously or intramuscularly. Finally, improving postoperative care will reduce perioperatively mortality to a greater extent than reducing intraoperative anaesthesia-related complications.

Choosing general versus regional anesthesia for the elderly.

Although clinical perceptions and theoretic considerations suggest regional anesthesia should be safer than general anesthesia in elderly patients, current studies indicate no difference in outcomes. Regional anesthesia may still prove superior to general anesthesia if the right patient population or right endpoints are identified for comparison. A study of consequence of outcome, comparing the two approaches has created an expansion of the definition of anesthesia-related complications.

Electroencephalographic evidence of arousal in dogs from halothane after doxapram, physostigmine, or naloxone.

The clinical impressions of enhanced arousal from halothane anesthesia and improvement of postanesthesia recovery scores after doxapram, physostigmine, or naloxone have not been verified in laboratory studies based on the effect of these drugs on MAC. With induction of anesthesia, a shift in the amplitude of the EEG from low to high occurs at anesthetic concentrations well below MAC and appears to coincide with the loss of consciousness. The authors examined the effect of arousal agents on the end-tidal halothane concentration required to produce this shifting EEG. In 24 unmedicated dogs, the end-tidal halothane concentration was elevated to 20 per cent above the shift point concentration (from 0.61 +/- 0.03 to 0.73 +/- 0.03 per cent) and maintained at this level for 30 min. Doxapram, 1 mg/kg, iv, and physostigmine, 0.03 mg/kg, iv, converted the EEG from a high amplitude to a low amplitude tracing in 22 +/- 3 s in eight of eight, and 225 +/- 37 s in seven of eight dogs, respectively. The end-tidal halothane concentration required to restore the shifting EEG was elevated above control for 50 +/- 7 min and 109 +/- 7 min, respectively. Naloxone, 0.06 mg/kg, iv, produced an awake EEG in two of eight dogs in 233 +/- 18 s which persisted for 22 +/- 4 min, and a transiently shifting EEG in three of eight dogs between 200 and 240 s. Naloxone 0.006, mg/kv, iv, produced an awake EEG in 80 +/- 8 s in four of four dogs who had previously received doxapram 3 h earlier. In this model doxapram and physostigmine paralleled the clinically observed onset and duration of arousal. The inconstant arousal from halothane anesthesia induced by naloxone was interpreted in terms of an opiate receptor independent action.

Hypertensive response to thiopental in man during cardiopulmonary bypass.

We report the effect of 250 mg of sodium thiopental on vascular tone at constant blood flow in 26 patients undergoing cardiopulmonary bypass while the ascending aorta was cross-clamped. Light anaesthesia was effected with fentanyl and enflurane, muscle relaxation with pancuronium. After a latent period of 10.5 +/- 0.7 s there was a hypertensive response of 9.8 +/- 0.5 s duration and of 21.4 +/- 1.7 mmHg (2.8 +/- 0.2 kPa) magnitude; this was followed by hypotension of 39.6 +/- 4.2 s duration and of 18.4 +/- 1.9 mmHg (2.4 +/- 0.3 kPa) magnitude. There was a statistically significant inverse correlation between the hypertension and body temperature (P = 0.005); the time to onset of hypertension correlated directly with pump volume (P = 0.001), weight of the patient (P = 0.03), and cross-clamp time before the drug was given (P = 0.002), and correlated inversely with the serum sodium concentration (P = 0.001). The duration of hypertension was inversely related to the plasma bicarbonate (P = 0.01) and body temperature (P = 0.04). The duration of hypotension was significantly longer in women (P = 0.0001) and was directly related to the duration of cross-clamping (P = 0.0007), to pH (P = 0.0016), and to PCO2 (P = 0.04). We speculate that thiopental induced the hypertensive response due to a potentiation of the vasoconstrictive (local) effect of norepinephrine, and induced the hypotensive response by a central nervous system effect. Thiopental had no apparent effect on venous tone.

Sagittal diameter of the cervical canal in normal Indian adults.

This paper is based on a radiographic study of 300 normal individuals from 18 to 34 years of age comprising 207 males and 93 females. A lateral radiograph of the cervical spine with a focal-film distance of 6 ft was obtained of each subject to measure the sagittal diameter of the cervical spinal canal. The mean sagittal diamter ranged from 21.43 mm at C1 to 16.42 mm at C7 in males and from 20.13 mm at C1 to 15.54 mm C7 in females. This diameter decreased from C1 down to C4 or C5 where there was a gradual but marginal increase to C6. This diameter was smallest at C7. In general the sagittal diameters In females were about 1 mm less than in males at all vertebral levels. The smallest sagittal diamter from C3 to C7 in both sexes was 13 mm. The largest sagittal diameter varied from 20.5 to 28 mm in males and 18.5 to 26 mm in females. The mean sagittal diameter showed some relationship to height in males. No significant difference was observed in relation to weight. The posterior component of the sagittal diameter was smaller in females than in males due to a difference in development of the laminae.

Somatostatin, anaesthesia, and the carcinoid syndrome. Peri-operative administration of a somatostatin analogue to suppress carcinoid tumour activity.

A patient with carcinoid syndrome on long-term antiserotonin therapy with parachlorophenylalanine, experienced a flushing attack with hypotension during the prophylactic administration of aprotonin prior to the induction of anaesthesia. When she was subsequently prepared with a long-acting somatostatin analogue, octreotide (Sandostatin, Sandoz SMS 201-995), plasma levels of tumour-released hormones were reduced and anaesthesia for resection of hepatic metastases was uneventful. The advantages of an anaesthetic approach based on inhibition of carcinoid tumour activity, rather than antagonism of released hormones, are discussed.

Effect of pethidine, fentanyl and morphine on post-operative shivering in man.

One hundred consecutive patients who shivered following general or regional anesthesia and a surgical procedure were randomly treated with 25 mg pethidine, 2.5 mg morphine, 25 micrograms fentanyl or sodium chloride 0.9%, given in equal intravenous volumes over a 15-min period. The effects were evaluated every 5 min after the first injection. There was a spontaneous, time-related disappearance of shivering in the sodium chloride-treated patients. In the pethidine-treated group, shivering disappeared more than twice as fast as in the control group. The difference was highly significant at 15 and 20 min (P less than 0.001) and was unrelated to weight, body temperature or duration of anesthesia. Women responded sooner than men, reaching significance at 10 min (P less than 0.05), while men did so only at 20 min. Morphine or fentanyl had no effect. Nausea and vomiting were minimal and of equal incidence in narcotic- and placebo-treated patients.

The direct effects of propofol on myocyte contractile function after hypothermic cardioplegic arrest.

Propofol is being used more often in cardiac surgery, particularly after hypothermic, hyperkalemic cardioplegic arrest (HHCA). The purpose of this study was to examine the effects of propofol on isolated myocyte contractile function under both normothermic conditions and after simulated HHCA and rewarming. Myocytes were isolated from the left ventricle of eight pigs. Myocyte contractile function was measured under both normothermic conditions and after simulated HHCA (incubation at 4 degrees C for 2 h in crystalloid cardioplegia; K+ = 24 mEq/L) using computer-assisted videomicroscopy in the presence of 2, 4, and 6 micrograms/mL propofol (11.2, 22.4, and 33.6 microM/L, respectively). Isoproterenol (25 nM) was then added and contractile function measurements repeated. Propofol caused significant dose-dependent reductions in myocyte velocity of shortening (baseline = 67 +/- 2 microns/s; propofol = 2 micrograms/mL, 45 +/- 4 microns/s; and propofol = 6 micrograms/mL, 27 +/- 3 microns/s; P < 0.05). HHCA and rewarming caused a significant reduction in myocyte velocity of shortening (29 +/- 0.9 microns/s, P < 0.05), with further significant dose-dependent reductions in contractile function after the addition of propofol. Propofol caused a decrease in beta-adrenergic responsiveness under normothermic conditions, but not after simulated HHCA. Results from the present study demonstrated for the first time that the reduction in isolated myocyte contractile function after simulated HHCA is further decreased by propofol administration.

The direct and interactive effects of phosphodiesterase inhibition and beta-adrenergic stimulation on myocyte contractile function after hypothermic cardioplegic arrest.

The direct and interactive effects of phosphodiesterase inhibition (PDEI) and beta-adrenergic receptor (beta AR) stimulation on isolated myocyte contractile function were examined after hypothermic, hyperkalemic, cardioplegic arrest (HHCA) and under normothermic conditions. Left ventricular (LV) myocytes were isolated from porcine hearts and myocyte contractile function was measured under normothermic conditions (37 degrees C in standard media) and after HHCA (2 h at 4 degrees C in Ringer's solution with 24 mEq KCl) with subsequent rewarming. Myocytes were then randomly assigned to treatment with the beta AR agonist isoproterenol (25 nM), the phosphodiesterase inhibitor amrinone (50 microM), or a combination of these compounds and contractile function measurements repeated. Baseline myocyte contractile function was reduced by 32% after HHCA. Isoproternol alone increased myocyte contractile function more than 100% under both normothermic conditions and after HHCA, whereas amrinone alone significantly (60%) improved myocyte contractile function only after HHCA. Amrinone preincubation followed by isoproterenol improved contractile function after HHCA to a greater extent than all other treatment protocols. In contrast, combination treatment under normothermic conditions did not augment myocyte contractile function relative to isoproterenol alone. These findings suggest that amrinone has differential effects on contractile processes. Moreover, the marked improvement of contractile function after HHCA with PDEI pretreatment followed by beta AR stimulation may have implications in treatment strategies for improving myocardial function after cardiopulmonary bypass and provide insight into contractile dysfunction after HHCA.

Preservation of myocyte contractile function after hyperthermic cardioplegic arrest by activation of ATP-sensitive potassium channels.

BACKGROUND: Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of KATP channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function. METHODS AND RESULTS: Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37 degrees C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 micromol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33+/-2 versus 66+/-2 microm/s, P<.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58+/-4 microm/s, P<.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147+/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109+/-4 nmol/L, P<.05). CONCLUSIONS: Cardioplegic arrest with simultaneous activation of KATP channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.

Negative and selective effects of propofol on isolated swine myocyte contractile function in pacing-induced congestive heart failure.

BACKGROUND: Although propofol (2-6 di-isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations. METHODS: Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micron/s) was examined in myocytes from five control pigs and in five pigs with pacing-induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1-6 micrograms/ml. In addition, myocyte contractility in response to beta-adrenergic receptor stimulation (isoproterenol, 10-50 nM) in the presence of propofol (3 micrograms/ml) was examined. RESULTS: Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end-diastolic diameter (control 3.3 +/- 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/- 3% vs. CHF 12 +/- 2%, P < 0.05). Propofol (6 micrograms/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 microns/s vs. 27 +/- 3 microns/s; P < 0.05) and CHF myocytes (29 +/- 1 microns/s vs. 15 +/- 1 microns/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 microgram/ml). beta-adrenergic responsiveness was reduced by propofol (3 micrograms/ml) in control myocytes only. CONCLUSIONS: Propofol has a direct and negative effect on basal myocyte contractile processes in the setting of CHF, which is more pronounced than that on healthy myocytes at reduced propofol concentrations.