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Biomedical subjects

B Drenger

Publications and source records attributed to B Drenger.

At least 37 records · Page 2Linked to original sources

Effect of halothane on sarcolemmal calcium channels during myocardial ischemia and reperfusion.

The present results provide indirect support for other studies which showed that halothane inhibited the Ca2+ accumulation associated with myocardial ischemia in isolated guinea pig hearts (6), demonstrating a potentially beneficial effect of the anesthetic on the ischemic heart. The role of halothane in preventing ischemia-induced dysrhythmias and attenuation of free radical generation on reperfusion offers a new potential use during open heart surgery. The method of continuous perfusion of oxygenated blood cardioplegia, retrogradely, through the coronary sinus, enables a concomitant administration of the VA before and during the ischemic period of the cardiopulmonary bypass. Further studies may promote the use of the volatile anesthetic when myocardial ischemia and reperfusion are present during open heart surgery.

Animals↗

Halothane modifies ischemia-associated injury to the voltage-sensitive calcium channels in canine heart sarcolemma.

BACKGROUND: Recent experimental data suggest that functional and metabolic changes in the myocardium caused during ischemia and subsequent reperfusion may be attenuated by the volatile anesthetics through the prevention of intracellular calcium accumulation. The main purpose of the current research is to identify a mechanism responsible for the alterations of ischemia-associated injury to the voltage-sensitive Ca2+ channels (VSCC) in the sarcolemma during halothane anesthesia. METHODS: The effect of 10 min myocardial ischemia in canine heart and 20 min reperfusion on the function of the VSCC in the sarcolemma was examined in the presence or absence of 1.6 vol% halothane administered in vivo. The membranes were isolated through differential centrifugation/filtration from the ischemic (left anterior descending territory) and normally perfused myocardium. Comparison of binding characteristics in the ischemic and nonischemic zones was made using equilibrium-binding studies of a dihydropyridine calcium channel blocker, [3H]isradipine (0.05-1.0 nM), to the VSCC in the sarcolemma. Control studies were performed on membranes prepared from the same perfusion zones, but from hearts who were not exposed to ischemia. RESULTS: The control studies (n = 5) showed no difference in binding kinetics between the different zones in the heart. After 10 min of ischemia, a 50 to 95% increase in specific [3H]isradipine binding to the sarcolemmal membranes was observed as compared to control membranes (P < 0.001). The maximal binding capacity (Bmax) increased by 85%, whereas the dissociation constant (Kd) remained unchanged. In the reperfusion experiments, a moderately increased binding (of 32%) was observed with a 40% increase in Bmax (P = NS). In the presence of 1.6% inhaled halothane, the effect of ischemia was attenuated. A decrease of 32.1% to 41.8% in equilibrium binding was observed (31% decrease in Bmax; P < 0.03 and 0.02, respectively). CONCLUSIONS: Even a brief period of myocardial ischemia produces a marked increase in the available high-affinity binding sites in the VSCC, a finding that is well correlated with previous experimental observation of increased calcium ion influx to the myocardial cell. On reperfusion, some recovery of the ischemic changes in the VSCC was evident. The binding kinetics which characterize this early phase of cell injury were reversed by halothane anesthesia, indicating a possible reduction in calcium entry, which may represent one of the beneficial effects of the anesthetic in the ischemic heart.

Animals↗

Warm blood cardioplegia for patients undergoing revascularization for left main coronary artery disease.

Between February 1991 and June 1992, 62 patients (50 males) underwent coronary artery bypass (CAB) operation for significant left main coronary artery disease. Age varied between 47 and 81 years. 53 patients had unstable angina, 16 had recent myocardial infarction, and 16 had heart failure. 22 patients were in functional capacity class IV (Canadian Heart Association) and 2 patients were in unstable hemodynamical condition before the operation. Intraaortic balloon pump was inserted before the operation in 3 patients. Six patients had previous CAB surgery. All the patients were operated using myocardial protection with warm blood cardioplegia, given antegradely and retrogradely in 58 and only antegradely in 4 patients. Body temperature was maintained at 30 +/- 1.8 degrees C. Number of distal anastomoses averaged 4.3 +/- 0.9. One patient underwent additional resection of a left atrial myxoma and another aortic valve replacement. LIMA (left internal mammary artery) was used to bypass the LAD in 58 (94%) patients. Early mortality was 3 cases (4.8%). Major and minor postoperative complications occurred in 17 patients. These data suggest that warm blood cardioplegia provides superior myocardial protection in patients with left main coronary artery disease.

Aged↗

Dose-response effect of intrathecal alfentanil on canine lower urinary tract dynamics.

The effect of intrathecal (IT) administration of three different doses (1, 2.5, and 5 micrograms/kg) of alfentanil on lower urinary tract dynamics was examined by urodynamic studies, cystometrograms (CMG), and urethral pressure profiles (UPP) in seven anesthetized dogs. Simultaneous serum drug concentrations were determined by specific radioimmunoassay for time-response analysis. A significant dose-dependent relaxation of urethral musculature expressed by a reduction in UPP values of 41.5% and 38.4% (P < 0.03) was noted 30 min after 5 and 2.5 micrograms/kg IT alfentanil, respectively, whereas the decrease of 13.4-22% in mean CMG values was not significant. All changes in UPP and CMG returned to baseline values by 60 min. The pharmacokinetics of alfentanil from the cerebrospinal fluid to the systemic circulation were linear, i.e., dose-independent with maximal serum concentrations of 0.6, 1.4, and 3.5 ng/mL 10 min after the three respective IT doses. The low serum alfentanil concentrations and the lack of time correlation between the peak values and the changes in urinary tract activity, point to a spinally mediated mechanism. The short-lived effect of IT alfentanil on lower urinary tract dynamics and the relaxation of the bladder neck allow for unobstructed micturition pathways and may avoid urinary retention.

Alfentanil↗

Spinal cord stimulation evoked potentials during thoracoabdominal aortic aneurysm surgery.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Depression of calcium channel blocker binding to rat brain membranes by halothane.

The present study evaluates the action of volatile anesthetics on the voltage-dependent Ca2+ channels in isolated rat brain membranes, measured as changes in binding of the Ca2+ channel blocker [3H]isradipine to these membranes. Equilibrium binding studies with increasing concentrations of [3H]isradipine (0.01-1 nM) in the presence of halothane (1.9%), isoflurane (2.3%), and enflurane (4.8%) at 25 degrees C were performed. Only halothane produced a significant depression in the specific binding of isradipine to the brain membranes at 0.5 and 1.0 nM [3H]isradipine (P = 0.028 and 0.018, respectively). Isoflurane and enflurane had such inconsistent effects that the data were inconclusive. Halothane produced a significant dose-dependent inhibition of binding, the maximum inhibition being 44% (P less than 0.005). Nonlinear regression analysis fit of the binding data indicates halothane produced a 48% decrease (P less than 0.05) in the maximal number of binding sites (Bmax) with no effect on the dissociation constant (Kd). As voltage-dependent Ca2+ channels are important in mediating neurotransmission, the marked decrease in channel number (Bmax) associated with halothane exposure suggests that this phenomenon might be related to the mechanism of general anesthesia.

Animals↗

Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia.

Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms.

Adult↗

Volatile anesthetics depress calcium channel blocker binding to bovine cardiac sarcolemma.

Volatile anesthetics produce their negative inotropic effect on the heart mainly by interference with calcium homeostasis in the myocardial cell. In order to elucidate the mechanism of the depression, we have evaluated the effect of the volatile anesthetics on the binding of the calcium channel blocker [3H]nitrendipine to purified bovine cardiac sarcolemma. The radioligand binding studies were carried out at 25 degrees C, with increasing concentrations of [3H]nitrendipine (0.01-1 nM), in the presence or absence of unlabeled nitrendipine to determine specific binding, and with or without 1.9% halothane, 2.3% isoflurane, and 4.8% enflurane. Separately, [3H]nitrendipine was measured in the presence of increasing doses of halothane (0.78, 1.33, 1.90, and 2.57%). Kinetic studies of association and dissociation rate were performed with 1.90% halothane and 1 nM [3H]nitrendipine at different time intervals. All three volatile anesthetics produced depression of [3H]nitrendipine binding to the isolated cardiac sarcolemma. Only halothane produced a significant depression in binding, ranging between 59 and 66% (P less than 0.05), depending on the concentration of [3H]nitrendipine used. Isoflurane produced 29-38% depression, and enflurane produced 5-22% depression. Halothane also produced a significant (P less than 0.01) dose-dependent decrease in [3H]nitrendipine-specific binding. The kinetic binding experiments demonstrated that the time course for halothane's effect on association and dissociation of [3H]nitrendipine was 5 min for the half-maximum effect; the maximal reduction in binding capacity was at 15-30 min (P less than 0.05). Scatchard analysis revealed that all three volatile anesthetics produced reduction in the maximal number of binding sites; however, they varied in their effect on binding affinity. Only halothane produced a homogenous increase in the dissociation constant, signifying reduced affinity of the Ca2+ blocker to the channel. We suggest that the volatile anesthetics produce conformational changes in these channels consistent with their ability to depress channel-mediated Ca2+ influx into myocytes.

Anesthetics↗

Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal aneurysm surgery.

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings.

Aorta, Abdominal↗

Urodynamic studies after intrathecal administration of baclofen and morphine in dogs.

The effects of intrathecally administered baclofen and morphine on the lower urinary tract dynamics of anesthetized dogs were investigated by means of cystometrogram and urethral pressure profile measurement. The experiments were performed prior to and 30, 60 and 90 minutes following intrathecal injection of either baclofen (0.03 mg./kg.), morphine (0.03 mg./kg.), or a mixture of the two (0.03 mg./kg. of each drug). Vesical pressure was significantly depressed after either baclofen (p less than 0.005) or morphine (p less than 0.005), while urethral pressure was decreased significantly only following baclofen (p less than 0.025). Administration of a baclofen/morphine admixture resulted in an additive reaction on the urethral pressure profile, compared with the changes brought about by each drug alone. Relaxation of the bladder and reduction in urethral resistance occurred 30 minutes post injection, increasing progressively after 60 and 90 minutes. The results demonstrated that baclofen, by its influence on cord neuron interaction, is capable of inhibiting the activity of the smooth muscle of the normal bladder and urethra, which in the case of the latter became more pronounced when both drugs were administered simultaneously by the intrathecal route.

Animals↗

Extradural bupivacaine and methadone for extracorporeal shock-wave lithotripsy.

Combined extradural bupivacaine and methadone analgesia was investigated in 144 patients who underwent extracorporeal shock wave lithotripsy (ESWL). Patients were assigned randomly to one of three groups: group I--extradural 0.5% bupivacaine hydrochloride 0.75 mg kg-1; group II--extradural 0.1% methadone hydrochloride 4 mg after the bupivacaine; group III--as group II, plus a continuous extradural infusion of methadone 0.3 mg h-1 after operation. In all patients, only partial motor deficit occurred. During ESWL, patients who received extradural bupivacaine and methadone had significantly less pain compared with those who had bupivacaine alone (P less than 0.025). Extradural anaesthesia and immersion in the warm water bath were accompanied by only mild fluctuations in arterial pressure. After ESWL, significantly more patients with continuous methadone infusion were pain free (P less than 0.05) and they required less systemic analgesics. The anaesthesia during and after the ESWL procedure may be carried out safely and effectively by the administration of small doses of bupivacaine combined with methadone followed by infusion of the opioid.

Analgesia, Epidural↗

Epidural methadone for analgesic management of patients with conservatively treated proximal femoral fractures.

Epidural methadone analgesia was initiated soon after admission to emergency room in elderly patients who sustained osteoporotic proximal femoral fracture and who were considered to be high surgical risks. The severe pain was significantly reduced, enabling early mobilization of the patients. The analgesia was discontinued only when nonnarcotic analgesia sufficed. The treatment lasted for about 3.5 weeks. One minor complication was observed during the treatment period. We concluded that patients who have femoral neck fracture who are at high risk for operation and have to be observed and stabilized before operation can be managed by continuous epidural methadone analgesia.

Aged↗

Urodynamic studies after intrathecal fentanyl and buprenorphine in the dog.

Cystometrograms (CMG) and urethral pressure profiles (UPP) were used in six anesthetized dogs to study the urodynamic effects of intrathecal (IT) injections of fentanyl and buprenorphine. The CMG and UPP were examined for each of the two drugs in all dogs (four experiments per animal). The measurements were performed before and 15, 30, 60, 90, and 120 min after IT injection of either 1.5 micrograms/kg fentanyl or 2 micrograms/kg buprenorphine. Fifteen minutes after IT injection of fentanyl, reduction in bladder tone was already noted, followed by decreases in mean peak vesical pressure of 48.3% +/- 6.0 (SE) (P less than 0.05) and mean peak urethral pressure of 38% +/- 3.0 (P less than 0.05) between 30 and 60 min after injection. These decreases, occurring in each experiment, gradually lessened at 90 and 120 min. The effects of IT buprenorphine, a partial opioid agonist, on bladder and urethral dynamics were inconsistent and non-significant in all studies. Disturbances of micturition observed clinically after spinal opioid administration may be related to the decrease in intravesical pressure and the resulting highly compliant bladder. Relaxation of the urethral musculature seen 15 min after IT fentanyl may prevent overdistension of the bladder and its associated complications.

Animals↗

Attenuation of ocular and systemic responses to tracheal intubation by intravenous lignocaine.

This study was undertaken to determine whether intravenous lignocaine could mitigate or prevent the ocular reactions and especially the acute increase in intraocular pressure associated with laryngoscopy and tracheal intubation. Two groups of children undergoing minor eye surgery under nitrous oxide-oxygen-halothane anaesthesia were examined. The experimental group (n = 17) received 2 mg/kg lignocaine and the controls (n = 18) an equivalent volume of saline. The incidence of local laryngeal and ocular reflexes was much lower in the lignocaine group. Pulse acceleration was significantly lower in the lignocaine group (p less than 0.025), and the maximal mean intraocular pressure was significantly less than in the control group (p less than 0.005). Other ocular reactions were recorded, and all were attenuated after lignocaine administration. The beneficial effects of lignocaine, a suppressant of autonomic reflexes, suggest that intraocular pressure, like the heart rate, rises after intubation as a result of autonomic stimulation. The use of intravenous lignocaine is thus recommended for children at risk, such as those needing an urgent operation because of lacerated eye injury under rapid sequence induction of anaesthesia.

Child↗