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Biomedical subjects

J X Mazoit

Publications and source records attributed to J X Mazoit.

At least 19 recordsLinked to original sources

Effects of halothane on the membrane potential in skeletal muscle of the frog.

Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical doses of halothane on V(m), recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. We assessed the mechanism of effects of superfused halothane on V(m) by the administration of selective antagonists of membrane bound Na(+), K(+) and Cl(-) channels and by inhibition of SR Ca(2+) release. Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V(m). The halothane-induced transient depolarization was sensitive to ryanodine (10 microM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). The hyperpolarization of V(m) induced by halothane (0.1 - 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 microM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 microM), charybdotoxin (CTX, 1 microM), and glibenclamide (10 nM). Our observations revealed that the effects of halothane on V(m) may be related to the increase in intracellular Ca(2+) concentration produced by the ryanodine-sensitive Ca(2+) release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca(2+)-dependent Cl(-) (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca(2+)-dependent K(+) channels, blocked by CTX, and to the opening of ATP-sensitive K(+) channels, inhibited by glibenclamide.

Anesthetics, Inhalation↗

Binding of propofol to blood components: implications for pharmacokinetics and for pharmacodynamics.

AIMS: Propofol is a widely used i.v. anaesthetic agent. However, its binding properties to blood components have not been fully studied. METHODS: We studied the binding of propofol to erythrocytes, to human serum and to isolated serum proteins. Because propofol bound to ultrafiltration and equilibrium dialysis membranes, we used a co-binding technique with dextran coated charcoal and with erythrocytes. RESULTS: Propofol free fraction in blood was 1.2-1.7% at total concentrations ranging from 2.80 to 179 microM (0.5 to 32 microg ml(-1)). Fifty percent was bound to erythrocytes and 48% to serum proteins, almost exclusively to human serum albumin. In the clinical range of concentrations (0.5-16 microg ml(-1)) 40% of the molecules bound to erythrocytes are on the red blood cells membranes. No binding to lipoproteins occurred and binding to alpha1-acid glycoprotein was less than 1.5% CONCLUSIONS: We conclude that hypoalbuminaemia may increase propofol free fraction particularly during prolonged administration. Since propofol is non-restrictively cleared, no change in clearance is expected to occur, and the increase in free fraction will not be compensated by a parallel increase in clearance. It is also noted that many in vitro studies used concentrations 50 to 500 times the concentration expected to be encountered in the immediate cellular environment.

Adult↗

Haemodynamic changes associated with portal triad clamping are suppressed by prior hepatic pedicle infiltration with lidocaine in humans.

Portal triad clamping (PTC) reduces venous return of blood to the heart. However, the decrease in cardiac index (CI) is associated with an unexpected increase in mean arterial pressure (MAP) and the 40% increase in systemic vascular resistance is greater than anticipated in compensation for the 10% decrease in CI. We hypothesized that a reflex elicited in the peritoneum accounted for this unanticipated haemodynamic response. Twenty patients undergoing liver resection were allocated randomly to have hepatic pedicle infiltration before PTC with either lidocaine 200 mg or placebo. MAP was recorded, and plasma osmolality and plasma concentrations of vasopressin, epinephrine, norepinephrine, dopamine, renin and endothelin were measured. After PTC, MAP increased significantly in the placebo group but decreased significantly in the lidocaine group. Plasma concentrations of vasopressin, epinephrine and norepinephrine increased significantly in the placebo group. Plasma concentrations of vasopressin decreased significantly in the lidocaine group, while plasma concentrations of epinephrine and norepinephrine were unchanged. A subsequent study in eight patients found that neither haemodynamic nor hormonal changes associated with PTC in the placebo group were altered by administration of lidocaine 200 mg i.m. before PTC.

Adolescent↗

The age-related effects of epidural lidocaine, with and without epinephrine, on spinal cord blood flow in anesthetized rabbits.

UNLABELLED: The effect of epidural or spinal epinephrine when added to local anesthetics on spinal cord blood flow (SCBF)are controversial. We evaluated the effects of epidural lidocaine, with or without epinephrine, on spinal cord blood flow in young and adult rabbits receiving 2% plain lidocaine, 2% lidocaine with epinephrine (1:200,000), or saline epidurally. Colored microspheres were injected through the left ventricle 10 min before and 7.5 and 30 min after epidural injection. The organs (brain, heart, kidneys, and the L6-7 segment of the spinal cord) were analyzed for regional blood flow determination. A significant decrease in mean arterial pressure was observed after the administration of lidocaine, with or without epinephrine, in both adult and young animals compared with saline. SCBF did not change over time in adult rabbits. Conversely, a significant decrease in SCBF was observed in the two groups of young rabbits receiving lidocaine. This decrease correlated with the decrease in mean arterial pressure but did not correlate with the use of epinephrine. We conclude that any reduction in blood pressure occurring in pediatric patients receiving a combined epidural-general anesthetic may result in decreased SCBF. IMPLICATIONS: In young rabbits, any decrease in blood pressure was followed by a decrease in spinal cord blood flow, a decrease that did not correlate to the use of epinephrine and was not observed in adult animals. These data suggest that blood pressure should be monitored closely to promptly treat any decrease in blood pressure when combined epidural-general anesthesia is used in children.

Aging↗

The effect of a sciatic nerve block on the development of inflammation in carrageenan injected rats.

UNLABELLED: Neurogenic inflammation may participate in postoperative inflammatory pain. We evaluated, in the rat, the influence of a short and prolonged sciatic nerve block on carrageenan-induced inflammation, the time course of which may be compared to postoperative inflammation. A catheter was placed on the right sciatic nerve and injected with 0.5% bupivacaine with epinephrine (0.2 mL): one injection in the Short Block Group, and four injections performed at 90-min intervals in the Prolonged Block Group. In all groups, the two hind paws were then injected with carrageenan. The development of inflammation was evaluated in both hind paws by measurement of paw circumference (PC) before, and 1, 2, 3, 4, 6, and 24 h after carrageenan injection. Temperature of both hind paws was evaluated at the same time points. The vocalization threshold to paw pressure test (VTPP) of both hind paws was evaluated at 6, 8, 10, 12, and 24 h after carrageenan injection. The left hind paw was used for the Control Group. A Sham Group had a catheter placed on the sciatic nerve and injected with normal saline. Inflammation developed in the Control Group with a maximum increase of PC (32%) and temperature (14%) 4 h after carrageenan injection and a maximal reduction of VTPP (44%) at 6 h, reflecting mechanical allodynia. A similar evolution was observed in the Sham Group. In the Short Block Group, the nerve block did not influence the PC, the paw temperature, or the VTPP when compared with the Control Group. In the Prolonged Block Group, when compared with the Control Group, the increased PC was reduced throughout the 24 h (P < 0.0001). The maximal increase in PC at 4 h was limited to 23%, as compared with the precarrageenan value. This effect on PC did not persist at 24 h. Paw temperature was increased (P = 0.07) throughout the study in the Prolonged Block Group, as compared with the Control Group. The VTPP reduction was still limited in the Prolonged Block Group at 24 h, as compared with the Control Group (P < 0.0001). We conclude that a prolonged sciatic nerve block limits carrageenan-induced increase in PC and, subsequently, mechanical allodynia at 24 h in rats. IMPLICATIONS: Our study has shown that a prolonged (6 h) but not a short sciatic nerve block (90 min) can limit edema and related pain after carrageenan-induced inflammation in rat.

Anesthetics, Local↗

A comparison of two techniques for cervical plexus blockade: evaluation of efficacy and systemic toxicity.

UNLABELLED: We compared two techniques of cervical plexus blockade (CPB) for carotid endarterectomy. Cervical plexus nerve block was performed with a combination of bupivacaine and lidocaine, with injections at the C2-C3, C3-C4, and C4-C5 transverse processes in 11 patients (classical CPB) or with a single injection after localization of the cervical plexus with a nerve stimulator in 12 patients (interscalene CPB). Pain scores were obtained during block placement and at predetermined phases of the operation. Arterial blood was sampled before and 3, 5, 8, 10, 15, 25, 40, and 60 min after CPB for measurement of bupivacaine and lidocaine concentrations. Interscalene CPB was less painful than classical CPB. The techniques appeared equally effective. Patients in both groups required equivalent supplementation with IV fentanyl and additional local infiltration with lidocaine during the most painful stages of surgery. The maximal concentration of bupivacaine was lower in interscalene CPB compared with classical CPB (1.0 microg/mL versus 1.5 microg/mL, P < 0.01). The time required to reach the maximal concentration of bupivacaine was 15 (10-40) min in interscalene CPB and 10 (5-17) min in classical CPB (P < 0.05). Lidocaine maximal concentration was similar in both groups, however the time required to reach the maximal concentration was longer (P < 0.05) in interscalene CPB (15 [10-60] min) than in classical CPB (10 [8-20] min). We conclude that the interscalene CPB is as effective as the classical CPB as a regional technique for carotid endarterectomy and may be associated with a lower systemic absorption of bupivacaine. IMPLICATIONS: Cervical plexus blockade for carotid endarterectomy can be effectively performed with a single injection after localization of the cervical plexus with a nerve stimulator. This technique is simple and was associated with less systemic absorption of local anesthetic than the multiple-injection technique.

Aged↗

Streptococcus pneumoniae pneumonia in mice: optimal amoxicillin dosing predicted from a pharmacokinetic-pharmacodynamic model.

In an attempt to better understand the interaction of amoxicillin with Streptococcus pneumoniae in the lung, and to determine the parameters of therapeutic efficacy of the antimicrobial agent amoxicillin, we used a pharmacokinetic-pharmacodynamic model to describe the overall dose-effect relationship of amoxicillin against 12 strains of S. pneumoniae with penicillin minimum inhibitory concentrations ranging from <0.01 to 16 microg/ml in a neutropenic murine pneumonia model. We were able to correlate amoxicillin dosing, pharmacokinetics, and the temporal changes in bacterial count in lung. Moreover, survival rates measured in one strain at different dosing were significantly related to the number of bacteria in lung calculated from the pharmacokinetic-pharmacodynamic model. Disappearance of amoxicillin from the effect compartment appeared to be very slow and the rate constant (k(e0)) governing this process was significantly different between strains, ranging from 0.00131 to 0.03945 h(-1). These findings have two major implications: 1) after a single dose of amoxicillin, bacterial counts in lung rapidly decreased and the bacterial growth remained suppressed during a long period of time after cessation of exposure of microorganisms to amoxicillin; and 2) the duration of bacterial growth suppression was related to the intrinsic properties of S. pneumoniae strains rather than to host environment because k(e0) was significantly different between strains. These two premises clearly demonstrate that bacterial growth suppression is related to an in vivo postantibiotic effect. Furthermore, we have shown that the major determinant of amoxicillin in vivo bactericidal activity and therapeutic efficacy appeared to be the dose of amoxicillin because amoxicillin exhibits a rapid dose-dependent killing regardless of the S. pneumoniae strain. Our findings may have implications for the clinical use of amoxicillin. In view of our results, the guidance to increase the amoxicillin-loading dose in pneumococcal pneumonia appears to be immediately clinically relevant.

Amoxicillin↗

[Conventional techniques for analgesia: opioids and non-opioids. Indications, adverse effects and monitoring].

Morphine dosage must be carefully adapted in patients with renal failure or severe liver failure. The i.v. route is used for morphine titration in the post anaesthesia care unit (PACU), or for analgesia in children. Systematic (not on demand) intramuscular or subcutaneous morphine must be administered at intervals not longer than 4 hours. Dosage is best determined after i.v. titration in the PACU. Codeine, administered orally, is metabolised into morphine. Codeine has almost no effect in 7% of Caucasians and at least 15% of Asians. Nalbuphine, which has a sedative effect and a short half-life, is mainly used in children. Paracetamol (acetaminophen) is used orally or rectally, most often in combination with codeine. Paracetamol dosage is 60-90 mg.kg-1.d-1, including a 20 mg (orally), or 40 mg (rectally) loading dose. Its therapeutic ratio is low, with a potential hepatic toxicity. Dosage must be lowered in alcoholics or in patients under isoniazide therapy. Non-steroidal anti-inflammatory drugs are powerful antinociceptive agents. Their use must be restricted to the first 5 postoperative days. Their major contraindications are kidney failure, risk of gastrointestinal bleeding, coagulation disorders, allergy. They also have a marked morphine sparing effect and reduce therefore the respiratory depression induced by morphine.

Analgesics, Non-Narcotic↗

Increase in the chronically monitored cerebrospinal fluid pressure after experimental brain injury in rats.

The early effects of experimental brain injury with diffuse axonal lesions on intracranial pressure (i.c.p.), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) in rats have been already studied. The aim of this experiment was to examine the effects of brain injury on ICP, MAP and CPP during the first few days post-injury. In order to do that, an accurate technique of ICP measurement had to be developed. In a series of eight rats, a translumbar intrathecal catheter (TIC) was surgically introduced allowing repeated measurements of cerebrospinal fluid pressure (CSFP). Under anaesthesia, a second series of nine rats were equipped simultaneously with TIC and an intracranial fiberoptic device to measure ICP. Simultaneous measurements of CSFP and ICP were recorded for baseline values, than during and after jugular compression which was intended to induce an acute and significant increase in ICP. A third series of 53 rats having TIC received an experimental severe brain injury. MAP was measured non-invasively and CPP was calculated as CPP-MAP. CSFP, MAP and CPP were intermittently measured during 5-6 post-traumatic days and compared to the values obtained during ten control rats (SHAM). A clinical score was used to compare clinical condition. The results showed that the translumbar CSFP accurately measured ICP in rats having normal or acutely increased ICP. The experimental brain injury induced increased CSFP lasting up to 5-6 days, with increased MAP during the first 6 hours. CPP values were compromised at 24-48 hours. The clinical performance was reduced in the brain-injured rats. The translumbar technique of CSFP measurement reflected exact ICP in normal and acutely increased ICP in rats. Experimental brain injury with diffuse axonal lesions can increase lumbar CSFP in rats for many days.

Analysis of Variance↗

The effect of pneumoperitoneum on intraocular pressure in rabbits with alpha-chymotrypsin-induced glaucoma.

UNLABELLED: Increased intraperitoneal pressure is associated with physiological changes including alterations of intraocular pressure (IOP). We have previously shown that IOP is not adversely affected by increased intraperitoneal pressure up to 15 mm Hg in women with no preexisting eye disease. The aim of this study was to measure IOP changes associated with increased intraperitoneal pressure (up to 15 mm Hg) of 2 h duration in 12 rabbits with alpha-chymotrypsin-induced glaucoma. A reliable model of glaucoma was created by injecting alpha-chymotrypsin into the posterior chamber of the right eye in 12 rabbits. Thereafter, 5 of the 12 rabbits with glaucomatous eyes were treated with topical timolol. The left eye was used as a control. During pentobarbital general anesthesia, increased intraperitoneal pressure up to 15 mm Hg was created by intraperitoneal CO2 insufflation. Body temperature and expired CO2 were kept constant throughout the study. IOP measurements were made using an electronic pneumotonometer. IOP, mean arterial pressure, heart rate, and central venous pressure were recorded in head-up and head-down positions before, during, and after increased intraperitoneal pressure. The IOP of both eyes, in both treated and untreated rabbits, increased significantly from baseline only when increased intraperitoneal pressure associated with the head-down position resulted in a significant increase in central venous pressure. However, the IOP increase remained within the diurnal range. The major finding of this study is that, in a reliable model of glaucoma, CO2 pneumoperitoneum was associated with an increase in IOP when a head-down position was combined with pneumoperitoneum. IMPLICATIONS: In rabbits with alpha-chymotrypsin-induced glaucoma, increased intraperitoneal pressure (up to 15 mm Hg) resulted in a significant intraocular pressure increase when pneumoperitoneum was associated with the head-down position. However, the intraocular pressure increase remained within the diurnal range.

Adjuvants, Anesthesia↗

Application of HPLC to counting of colored microspheres in determination of regional blood flow.

Colored microspheres have become popular compared with radioactive microspheres because they do not use radioactivity. However, they suffer from a much greater variability in their determination. We have developed a new method for assaying the dye using high-performance liquid chromatography (HPLC) with internal standard. This technique permits accurate determination of < or = 400 spheres in rat blood, heart, kidney, liver, and brain with a relative error [coefficient of variation (CV)] < 10%. To date, only three colors (white, yellow, and red) may be used because, of the five colors tested, one (violet) served as internal standard and another (blue) exhibited marked degradation during extraction. Compared with the classical spectrophotometric technique, HPLC allows a three to five times improvement in reproducibility with a relative error significantly lower (P < 0.01) than with direct spectrophotometry. Although this new technique appears to be more time consuming than the classical method, its use seems to be preferable because of the improvement in measurement sensitivity.

Animals↗

Adverse effects of regional anaesthesia in children.

True complications of regional block procedures pertain to the performance of the block technique and the local anaesthetic. Such complications include lesions caused by the device used, and many of these complications can be avoided by using specifically designed devices.Complications related to the local anaesthetic solution mainly consist of local and systemic complications. Local toxicity has mainly been reported in adults following spinal administration of 5% lidocaine (lignocaine), a drug that is not usually used in children. Systemic toxicity consists of CNS and cardiovascular complications, methaemoglobinaemia and allergic reactions. Systemic toxicity has special features in children, especially in those <1 year old. Infants have a much higher free serum concentration of local anaesthetics than older children and adults, and are more prone to the deleterious effects of local anaesthetics. Additionally, as regional blocks are usually performed under general anaesthesia in children, signs of CNS toxicity may be concealed. Because of their higher heart rate, newborns and infants are thought to be more prone to the phasic block produced by tertiary amine agents such as bupivacaine than are adults. Serum concentrations at which bupivacaine (and etidocaine) exert cardiac toxicity seem to be similar to those producing CNS toxicity. As there is an increased threshold for CNS toxicity in infants plus an increased (or equal) sensitivity to bupivacaine cardiotoxicity, cardiac signs may not be preceded by any sign of CNS toxicity. Cardiac complications include: (i) arrhythmias with high degree conduction block, major QRS widening, torsade de pointes, and ventricular tachycardia related to re-entry phenomena; and (ii) major vascular collapse favoured by a concomitant decrease in the myocardial contractile force. Other complications of regional block procedures result from poor selection of agent, and inadequate safety precautions and monitoring of the patient, especially during the postoperative period. There are 2 other groups of disorders often reported as complications of regional anaesthetics: (i) effects that were not anticipated by the anaesthetist because of a lack of knowledge of all the consequences of the technique used; and (ii) complications attributed to a concomitant regional block procedure but with no established, sometimes even improbable, causal link with the regional technique. The overall morbidity of regional anaesthesia in children is low. Sound selection of local anaesthetics, insertion routes and block procedures, together with appropriate and careful monitoring, should prevent any major undesirable effects and enable regional anaesthesia to be a well tolerated and effective tool to overcome pain associated with minimal morbidity.

Anesthesia, Conduction↗

Correlation between in vitro and in vivo activity of amoxicillin against Streptococcus pneumoniae in a murine pneumonia model.

We studied the relationship between in vitro bacteriological parameters [minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and killing rate, defined as the reduction in the inoculum within 1, 3 or 6 hr] and in vivo activity of amoxicillin against 12 strains of Streptococcus pneumoniae, with penicillin MICs of < 0.01 to 16 micrograms/ml, in a cyclophosphamide-induced neutropenic murine pneumonia model. Dose-response curves were determined for amoxicillin against each strain, and three quantitative parameters of in vivo amoxicillin activity were defined, i.e., maximal attainable antimicrobial effect attributable to the drug [i.e., reduction in log colony-forming units (CFU) per lung, compared with untreated controls], dose required to reach 50% of maximal effect and dose required to achieve a reduction of 1 log CFU/lung. We demonstrated a highly significant correlation between the dose required to reach 50% of maximal effect and MIC (Spearman r = 0.98, P < .0001) or MBC (Spearman r = 0.95, P < .0001) for amoxicillin against strains of S. pneumoniae with a wide range of amoxicillin MICs (0.01-8 micrograms/ml). Significant correlations between the dose required to achieve a reduction of 1 log CFU/lung and MIC (Spearman r = 0.98, P < .0001) or MBC (Spearman r = 0.95, P < .0001) were also observed. In contrast, there were no significant correlations between the maximal attainable antimicrobial effect attributable to the drug and MIC, MBC or killing rate or between killing rate and the dose required to reach 50% of maximal effect or the dose required to achieve a reduction of 1 log CFU/lung. We conclude that in vitro susceptibility test results (MICs and MBCs) correlated well with in vivo amoxicillin activity against pneumococcal strains, including highly penicillin-resistant strains, in this animal model. Furthermore, these data suggest that the estimated MIC breakpoints for amoxicillin against S. pneumoniae would be 2 micrograms/ml for intermediate-resistant and 4 micrograms/ml for resistant, although this remains to be confirmed in clinical studies.

Amoxicillin↗

Clonidine and or adrenaline decrease lignocaine plasma peak concentration after epidural injection.

Clonidine is an alpha 2-adrenoceptor agonist increasingly used in combination with lignocaine for spinal or epidural anaesthesia because of a prolonged analgesic effect. Life adrenaline, it may decrease lignocaine peak concentration (Cmax), thus leading to decreased toxicity. However, the effects of clonidine on resorption of lignocaine into the systemic circulation from the epidural space remain to be established. We studied the pharmacokinetics of lignocaine after epidural injection of lignocaine with or without clonidine, adrenaline and both drugs. Total body clearance and apparent volume of distribution were similar in the four groups, but the maximum observed concentration (Cmax) was markedly increased in the plain solution group as compared with the other groups; (plain lignocaine: 7.15 +/- 2.04 micrograms ml-1, lignocaine + adrenaline: 3.11 +/- 136 micrograms ml-1, lignocaine + clonidine: 4.48 +/- 1.26 micrograms ml-1, lignocaine + adrenaline + clonidine: 4.06 +/- 1.42 micrograms ml-1 [mean +/- s.d.]). Our results show that, clonidine decreases lignocaine Cmax to the same extent as adrenaline.

Adolescent↗

Effects of carbon dioxide embolism with nitrous oxide in the inspired gas in piglets.

We have compared cardiorespiratory variables in anaesthetized piglets whose lungs were ventilated with oxygen in nitrous oxide (N2O group) or nitrogen (N group) after right ventricular carbon dioxide boluses (0.5 or 1 ml kg-1; n = 12) or slow graded injections (n = 6). Boluses affected all variables studied significantly (P < 0.05) except mean systolic arterial pressure. Significant changes in PE'CO2 (P = 0.012) and PaO2 (P = 0.048) values were observed in the N2O group. Changes in PaCO2 were related to volumes of injected carbon dioxide (P = 0.044). Boluses of 1.0 ml kg-1 induced severe circulatory collapse in two piglets in the N2O group. Slow embolization altered respiratory variables significantly (P < 0.001)). PaO2 decreased significantly in the N2O group (P < 0.0001). Mean pulmonary arterial pressure increased significantly over time (P = 0.001) and lasted longer in the N2O group (P < 0.05). Volumes and time required to induce a 50% increase in mean pulmonary arterial pressure differed significantly between groups (P < 0.05). We conclude that nitrous oxide worsened the effects of rapid and slow carbon dioxide emboli on cardiopulmonary variables. Rapid carbon dioxide embolism altered respiratory and haemodynamic variables, while slow carbon dioxide embolism changed only respiratory variables.

Anesthesia, General↗

Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart.

1. The reported incidence of myocardial contusion after blunt chest trauma varies from 16 to 76%. Of these patients, about 6% present a severe, life threatening contusion. We used an isolated heart preparation to examine the effect of lignocaine on myocardial performance after contusion. 2. Thirty hearts obtained from male New Zealand rabbits were perfused at constant flow according to the Langendorff technique and were divided into four groups. The following parameters were measured at frequent intervals for 60 min: mean coronary perfusion pressure (CPP), left ventricular diastolic pressure (LVDP), developed pressure (DP), dP/dtmax, dP/dtmin. 3. Group 1 (n = 6) served as control, group 2 (n = 7) received lignocaine for 20 min (15 microM for the first 10 min and 30 microM for the following 10 min), group 3 (n = 9) had a contusion leading to a 30-50% decrease in dP/dtmax and group 4 (n = 8) had the contusion and the lignocaine infusion was started 10 min after the contusion and stopped after 30 min. Lignocaine concentration was measured in the effluent. 4. Lignocaine alone moderately decreased contractility in group 2. In group 3, after contusion, DP, dP/ dtmax, and dP/dtmin were markedly decreased during the 60 min recording period. In group 4, lignocaine infusion rapidly restored contractility. DP, dP/dtmax and dP/dtmin returned towards their basal values. This improvement of contractility remained stable, even after lignocaine infusion was discontinued. 5. In our rabbit isolated heart preparation, lignocaine at a low therapeutic concentration was able to restore contractility after contusion. These results need to be confirmed by other studies but this may lead to promising therapeutic intervention.

Analysis of Variance↗