Myocardial tissue oxygen during coronary artery constriction and hypotension in dogs

BACKGROUND: Sodium nitroprusside (SNP) may decrease myocardial tissue oxygenation in dogs with normal coronary arteries. We compared SNP- with desflurane-induced hypotension on myocardial tissue oxygen and pH in dogs with left anterior descending artery constriction. METHODS: Twenty-four dogs were anesthetized with 8% desflurane for baseline anesthesia. Catheters were inserted into the femoral artery and vein and the coronary sinus. A flow probe and flow restriction device was placed on the left anterior descending (LAD) artery. A probe that measured myocardial oxygen pressure was inserted into the middle myocardium in the LAD region. Baseline measures were made of LAD artery flow, arterial and coronary sinus blood gases, and myocardial tissue gases. A 30% decrease in blood pressure was induced with SNP with unrestricted LAD flow (n=6) or when LAD artery flow was restricted by 30% from baseline (n=6). In separate dogs, a 30% decrease in blood pressure was produced with 14 +/- 1% desflurane with unrestricted LAD flow (n=6) or with baseline LAD artery flow restricted by 30% (n=6). RESULTS: During SNP-induced hypotension with no LAD constriction, LAD artery flow and coronary sinus oxygen tension increased but myocardial tissue oxygen tension (PmO2) decreased by 40%. When baseline artery flow was decreased by 30% by LAD constriction, SNP-induced hypotension decreased tissue oxygen pressure by 80%, and ischemic acidosis was produced. During unrestricted LAD artery flow or with a 30% flow restriction, desflurane-induced hypotension produced no significant change from baseline myocardial tissue oxygen tension or pH. CONCLUSION: During coronary artery constriction, desflurane-induced hypotension maintained myocardial tissue oxygenation and pH better than did SNP-induced hypotension. The divergence between tissue and coronary sinus oxygen tension during SNP suggests that arteriovenous shunting may occur.     

Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep

This paper reports the cardiovascular effects of intentionally toxic intravenous doses of lidocaine, bupivacaine, and ropivacaine and the mechanisms of death. Fatal doses of lidocaine, bupivacaine, and ropivacaine were established in sheep treated with successive daily dose increments of each drug. The mean fatal dose of lidocaine (+/- SD) was 1450 +/- 191 mg (30.8 +/- 5.8 mg/kg), that of bupivacaine was 156 +/- 31 mg (3.7 +/- 1.1 mg/kg), and that of ropivacaine was 325 +/- 108 mg (7.3 +/- 1.0 mg/kg); thus the ratio of fatal doses was approximately 9:1:2. In four out of four lidocaine-treated animals, respiratory depression with bradycardia and hypotension without arrhythmias were the causes of death. Three out of four bupivacaine-treated animals died after the sudden onset of ventricular tachycardia/fibrillation without hypoxia or acidosis; the fourth died in a similar manner to the lidocaine-treated animals. Three out of five animals given ropivacaine died in a manner resembling the fatal effects of lidocaine-treated animals, but unlike the lidocaine-treated animals, in all three sheep there were also periods of ventricular arrhythmias. The remaining two ropivacaine-treated sheep died as a result of the sudden onset of ventricular tachycardia/fibrillation. The mean percentages of the fatal dose found in the myocardium was 2.8 +/- 0.7 for lidocaine-treated animals, 3.3 +/- 0.9 for bupivacaine-treated animals, and 2.2 +/- 1.4 for ropivacaine-treated animals; the corresponding percentages in whole brain were, respectively, 0.71 +/- 0.01, 0.71 +/- 0.21, and 0.89 +/- 0.27.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

Adding bupivacaine to high-potassium cardioplegia improves function and reduces cellular damage of rat isolated hearts after prolonged, cold storage

BACKGROUND: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. METHODS: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. RESULTS: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. CONCLUSIONS: Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.     

Observations on 100 patients with continuous intraoperative monitoring of intramyocardial pH. The adverse effects of ventricular fibrillation and reperfusion

Intramyocardial pH and temperature data recorded in 100 patients undergoing cardiac operations were analyzed to elucidate the effects of ventricular fibrillation and reflow. All patients underwent a single period of aortic clamping. Systemic hypothermia (25 degrees C) and intermittent cold crystalloid K+ cardioplegia were employed for myocardial protection. Baseline myocardial pH was 6.88 +/- 0.03 at a temperature of 36.5 degrees +/- 0.2 degree C. During the period of hypothermic ventricular fibrillation prior to aortic clamping, ventricular fibrillation did not affect myocardial pH in 45 patients (Group 1). In 21 patients (Group 2), it caused a significant drop in intramyocardial pH despite cooling. Group 2 patients had a higher incidence of valvular heart disease and left ventricular hypertrophy. They also exhibited low intramyocardial pH values during the subsequent periods of aortic clamping and reflow, indicating inadequate myocardial protection. During the period of reflow, reperfusion acidosis (pH less than 6.8 at 32 degrees C) was encountered in 39 patients (Group B) as opposed to 37 patients (Group A) whose pH remained well above 6.8 during that period. Group B patients had a higher incidence of valvular heart disease and left ventricular hypertrophy, tended to have more ischemic anterior walls prior to cardiopulmonary bypass, sustained longer periods of aortic clamping, had intramyocardial pH evidence of suboptimal protection during aortic clamping, were affected more adversely by ventricular fibrillation during reflow, and tended to have a higher operative mortality. Thus: Depending on the underlying myocardial disease, the adequacy of protection during aortic clamping, and the conditions of reflow, intramyocardial pH in man can fall significantly during ventricular fibrillation and reflow. The metabolic correlate of injury with reflow is a reperfusion acidosis that can reach as low as pH 5.98. When encountered, reperfusion acidosis can be minimized by prompt defibrillation.     

Glyburide decreases myocardial oxygen pressure in dogs

BACKGROUND: Reports show that glyburide, an adenosine triphosphate sensitive potassium (K+ATP) channel blocker, will reverse the myocardial protective effect of inhalational anesthesia. We evaluated the effect of glyburide on myocardial tissue oxygen pressure (PmO2) in dogs anesthetized with desflurane. METHODS: Twelve dogs were anesthetized with 8% end-tidal desflurane for baseline anesthesia. A flow probe was placed on the left anterior descending (LAD) artery. A probe that measured PmO2 was inserted into the middle myocardium in the LAD region. After baseline measures, six dogs received i.v. 1 mg kg(-1) of glyburide and six dogs received sham vehicle treatment. After the glyburide or sham treatment, each dog received an i.v. infusion of adenosine 0.1 microg kg(-1) x min(-1), sodium nitroprusside (SNP) 2-4 microg kg(-1) x min(-1) and 14% end-tidal desflurane in random order. RESULTS: Glyburide decreased LAD artery flow from 59 +/- 9 ml min(-1) to 30 +/- 6 ml min(-1) (P < 0.05) and PmO2 from 44 +/- 16 mmHg to 30 +/- 9 mmHg (P < 0.05). Adenosine infusion increased LAD artery blood flow 180% in the sham-treated dogs but produced no change in the glyburide-treated dogs. Sodium nitroprusside infusion increased LAD artery flow and decreased PmO2 in both the glyburide- and sham-treated dogs. Desflurane (14%) did not reverse the glyburide-induced vasoconstriction but increased PmO2 to 38 +/- 20 mmHg (P < 0.05). CONCLUSION: Glyburide produced myocardial tissue hypoxia, which was not changed by adenosine, worsened by SNP and improved by 14% desflurane. The improvement in PmO2 with desflurane occurred without a change in myocardial blood flow.     

Brain compared to heart tissue oxygen pressure during changes in arterial carbon dioxide in the dog.

Myocardial tissue oxygen pressure (PmO2 ) and left anterior descending (LAD) artery blood flow were measured in dogs anesthetized with 1.5% isoflurane, and were then compared to brain tissue oxygen pressure (PbO2 ) and middle cerebral artery (MCA) blood flow during normocapnia, hypocapnia, and hypercapnia. A craniotomy was performed and a tissue probe (Codman, Inc.) that measures PO2, PCO2, and pH was inserted into the brain cortex in the MCA region (n = 8). Separately, after a thoracotomy, a probe was inserted into the middle myocardium of the left ventricle, within the distribution of the LAD, in eight dogs. Blood flow probes were placed on the LAD or MCA. Blood flow and tissue gases were measured during normocapnia (PaCO2 = 38 mm Hg), hypocapnia (PaCO2 = 26 mm Hg), and hypercapnia (PaCO2 = 53 mm Hg). Mean arterial pressure, heart rate, arterial gases, and pH were not different between brain and heart measurements. PbO2 was 21 +/- 9 mm Hg (mean +/- SD ), 40 +/- 16 mm Hg, and 47 +/- 11 mm Hg. PmO2 was 35 +/- 12 mm Hg, 40 +/- 14 mm Hg, and 48 +/- 15 mm Hg during hypocapnia, normocapnia, and hypercapnia respectively. During hypercapnia, LAD and MCA flow increased 50% and tissue oxygenation increased 20% ( P < .05). During hypocapnia, MCA flow and PbO2 decreased 50% ( P < .05), but LAD flow and PmO2 did not significantly change. These results indicated that LAD flow and myocardial PO2 were less responsive to hypocapnia than MCA flow and PbO2.     

Comparison of adenosine,isoflurane, and desflurane on myocardial tissue oxygen pressure during coronary artery constriction in dogs

OBJECTIVE: To compare adenosine-, isoflurane-, or desflurane-induced hypotension with and without left anterior descending (LAD) coronary artery constriction for the effects on myocardial tissue oxygen pressure (PmO(2)) in dogs. DESIGN: Prospective, randomized, nonblinded. SETTING: University teaching hospital. PARTICIPANTS: Male nonpurpose-bred dogs (n = 18). INTERVENTIONS: Dogs were anesthetized with 1.5% isoflurane (n = 12) or 8% desflurane (n = 6). A flow probe and balloon occluder were placed on the LAD artery. A probe that measured myocardial oxygen pressure was inserted into the middle myocardium in the LAD region. Myocardial oxygen consumption (MVO(2)) was calculated as LAD flow x arterial minus coronary sinus oxygen content. MEASURES AND MAIN RESULTS: Measures were made during hypotension produced by adenosine infusion, 2.8% isoflurane, or 14% desflurane with and without LAD constriction to decrease blood flow 30%. Without LAD artery constriction, adenosine infusion increased LAD flow 90% and MVO(2) 70%, 2.8% isoflurane produced no change in MVO(2), and 14% desflurane decreased MVO(2) 25%, but no treatment changed PmO(2). LAD artery constriction decreased PmO(2) 50% by itself. Adenosine infusion during LAD constriction decreased tissue oxygen pressure an additional 60%, 2.8% isoflurane produced no change, and 14% desflurane increased PmO(2) 100%. CONCLUSION: There was an inverse relationship between the effect of adenosine, 2.8% isoflurane, and 14% desflurane on MVO(2) and PmO(2) during ischemia. This is consistent with reports that increasing oxygen demand worsens myocardial ischemia.     

Blood and brain tissue gaseous strategy for profoundly hypothermic total circulatory arrest

Brain tissue carbon dioxide tension, pH, and oxygen tension were measured in dogs undergoing hypothermic circulatory arrest below 20 degrees C with three types of blood gas manipulation. During core cooling, dogs were given pure oxygen (group I, n = 8), 5% carbon dioxide in oxygen (group II, n = 10), or 7% carbon dioxide in oxygen (group III, n = 4). During core cooling, brain tissue carbon dioxide tension decreased significantly in group I. During circulatory arrest, carbon dioxide tension rose by 21.5 mm Hg in group I, 35.3 mm Hg in group II, and 57.0 mm Hg in group III, nearly doubling in each group. From the last 5 minutes of core cooling to the end of rewarming, carbon dioxide tension was significantly higher in groups II and III than in group I. Brain tissue pH fell by 0.33 to 0.35 during 60 minutes of circulatory arrest and did not recover in groups II and III. Brain tissue oxygen tension decreased significantly during the latter two thirds of the circulatory arrest period in all three groups. To reduce progressive tissue hypercapnia and acidosis during and after circulatory arrest, a more hyperventilatory manipulation of blood gases than that achieved by alpha-stat strategy was thought beneficial for core-cooling perfusion.     

Sodium nitroprusside-induced,but not desflurane-induced,hypotension decreases myocardial tissue oxygenation in dogs anesthetized with 8% desflurane

OBJECTIVE: To compare sodium nitroprusside (SNP)-induced hypotension with desflurane-induced hypotension for the effects on myocardial blood flow and tissue oxygenation in dogs. DESIGN: Prospective, randomized, crossover, nonblinded. SETTING: University teaching hospital. PARTICIPANTS: Male nonpurpose-bred hounds (n = 8). INTERVENTIONS: Dogs were anesthetized with 8% desflurane. Catheters were inserted into the femoral artery and coronary sinus. A flow probe was placed in the left anterior descending (LAD) branch of the coronary artery. A sensor that measured myocardial oxygen pressure (PmO(2)) was inserted into the myocardium of the left ventricle. Myocardial oxygen consumption (MVO(2)) was calculated as LAD flow x arterial - coronary sinus oxygen content. MEASUREMENTS AND MAIN RESULTS: Measurements were made at baseline blood pressure levels of 99 mmHg (measure 1), during hypotension to 62 to 66 mmHg using intravenous SNP or 14% desflurane (measure 2), and during SNP or 14% desflurane with blood pressure support using phenylephrine (measure 3). Each dog randomly received both hypotensive treatments, separated by 1 hour. Baseline measures were PmO(2) = 46 +/- 9 mmHg, LAD flow = 43 +/- 11 mL/min, and MVO(2) = 2.47 +/- 0.73 mL O(2)/min. During hypotension induced with SNP, PmO(2) decreased 30% (p < 0.05), LAD flow increased 40% (p < 0.05), and MVO(2) did not change. During hypotension induced with 14% desflurane, PmO(2) did not change, and LAD flow and MVO(2) decreased 25% and 40% (p < 0.05). Blood pressure support with phenylephrine increased LAD flow and MVO(2) but did not change PmO(2) during SNP or 14% desflurane treatment. CONCLUSION: SNP-induced hypotension produced myocardial vasodilation, but tissue oxygenation was impaired. PmO(2) was maintained during desflurane-induced hypotension.     

Elevated mid-myocardial oxygen tension in the fibrillating heart during cardiopulmonary bypass

Mid-myocardial tissue oxygen tension was measured in the left ventricular wall of the hearts of ten dogs by means of a Silastic tonometer implanted earlier. During cardiopulmonary bypass, myocardial PO2 was significantly higher in a spontaneously fibrillating heart (5.4 +/- 0.9 kPa) than during the initial beating period (3.7 +/- 0.5 kPa) or after defibrillation (4.0 +/- 0.7 kPa). In general, there was a tendency towards increased myocardial blood flow, elevated oxygen uptake and reduced coronary sinus oxygen content during ventricular fibrillation, compared with the situation in the beating heart. Myocardial lactate extraction remained unchanged during the different phases of cardiopulmonary bypass. The increase in mid-myocardial oxygen tension during ventricular fibrillation was probably due to increased total myocardial blood flow and redistribution of regional myocardial circulation. In two additional dogs, ventricular fibrillation resulted in left ventricular distension and a simultaneous fall of myocardial oxygen tension, which indicates the necessity of left ventricular decompression suction in a fibrillating heart during cardiopulmonary bypass.     

Effects of thoracic epidural anesthesia on myocardial pH and metabolism during ischemia

The effect of thoracic epidural anesthesia (TEA) on the ischemic myocardium was examined in open-chest dogs anesthetized intravenously. Ischemia induced by brief coronary artery occlusion caused an elevation of the ST segment in epicardial ECG and a reduction in myocardial pH and contractile force. TEA with 0.15 ml/kg of 0.4% bupivacaine solution attenuated an ischemia-induced decrease in myocardial pH and an increase of the ST segment in epicardial ECG. This attenuation was maintained even after the restoration of blood pressure and heart rate, which had been decreased significantly after TEA, to pre-TEA levels, suggesting that a beneficial effect of TEA should not be confined to its hemodynamic changes such as decreased blood pressure and heart rate. In contrast, the subendocardial contents of ATP, creatine phosphate (CP) and lactate were not affected by TEA, either in the presence or the absence of 5 min LAD occlusion. These results suggest that neither hemodynamic nor metabolic changes are responsible for the reduced myocardial ischemic acidosis induced by TEA after brief coronary artery occlusion. The acidosis-saving property of TEA is favorable for the ischemic heart.     

Evaluation of subcutaneous tissue gases and pH during induction of acidosis and alkalosis. An experimental study in pigs

Peripheral tissue oxygen utilization was studied during hypoxic-induced acidosis and sodium bicarbonate-induced alkalosis in 8 domestic pigs by measurements of subcutaneous oxygen tension (PscO2), carbon dioxide tension (PscCO2) and pH (pH(sc)) in relation to central hemodynamic parameters and oxygenation. Hypoxic-induced acidosis resulted in a decrease in P(sc)O(2) [corrected] and arterial oxygen tension (P(a)O(2)) to one third of baseline values (p < 0.05), an increase in PscCO2 and arterial carbon dioxide tension (PaCO2) from 41 to 55 and 34 to 39 mm Hg, respectively (p < 0.05), and a decrease in pH(sc) from 7.47 to 7.30 (p < 0.05). PscO2 and PaO2 increased during reversal of hypoxia and infusion of bicarbonate (p < 0.05), without reaching baseline values. In parallel PscCO2 decreased and pH(sc) increased but changes lagged behind changes in blood gases. Alkalosis established by further infusion of bicarbonate resulted in a decrease in PaO2 to 62 mm Hg whereas PscO2 remained below baseline values (p < 0.05). Correction of oxygen utilization in the subcutaneous tissue as measured by the markers PscCO2 and pH(sc) is slower than indicated by changes in tissue oxygen tension, blood gases and pH. Overcompensation of acidosis with bicarbonate resulting in alkalosis impairs oxygenation.     

Comparison of resuscitation of sheep and dogs after bupivacaine-induced cardiovascular collapse

This study evaluated interspecies sensitivity and ability to resuscitate pentobarbital anesthetized sheep and dogs after cardiovascular toxic doses of bupivacaine. Every minute, 3 mg/kg of bupivacaine was injected into the right atrium over the course of 10 sec until cardiovascular collapse occurred. While the bupivacaine was given, the animals were made apneic for 90 sec and then ventilated with 100% oxygen. After the bupivacaine administration, cardiovascular collapse occurred in the form of electromechanical dissociation progressing to asystole in dogs, whereas in sheep the predominant rhythm was ventricular fibrillation leading to asystole. Resuscitation was performed using open chest heart massage, bretylium for treatment of ventricular tachycardia and fibrillation, and epinephrine with atropine for treatment of electromechanical dissociation or asystole. The initial dose of bupivacaine used to cause cardiovascular collapse was 3.5 +/- 1.2 mg/kg in sheep and 24.6 +/- 8.5 mg/kg in dogs (P less than 0.01). All sheep and dogs were resuscitated from the first cardiovascular collapse. The resuscitation time was 2.1 +/- 1.0 min in dogs and 36.9 +/- 15.4 min in sheep (P less than 0.01). All dogs could be resuscitated after two additional cardiovascular collapses induced by bupivacaine, but no sheep could be resuscitated after a second cardiovascular collapse. Concentrations of bupivacaine in cardiac tissue and serum levels of bupivacaine after the last resuscitation attempt were significantly greater in the dogs than in the sheep. We conclude that sheep are more sensitive to bupivacaine than dogs, but that even sheep can be resuscitated after cardiovascular collapse produced by bupivacaine.     

Potentiation by mild hypothermia of ventricular conduction disturbances and reentrant arrhythmias induced by bupivacaine in dogs

High concentrations of bupivacaine and profound hypothermia individually cause intraventricular conduction disturbances and reentrant arrhythmias. The effects of the combination of relatively low concentrations of bupivacaine and mild hypothermia are unknown and are the subject of this study. Three groups (n = 10-12) of dogs anesthetized with thiopental-chloralose were treated as follows: group 1, bupivacaine + hypothermia; group 2, bupivacaine alone; group 3, hypothermia alone. Bupivacaine was administered as a 4 mg/kg iv bolus followed by an iv infusion of 0.1 mg.kg-1.min-1. Hypothermia, i.e., a 4 degrees C reduction in core temperature, was produced by cooling the blood with an extracorporeal circuit. The peripheral ECG was recorded to determine the duration of QRS complexes and the QT interval. Conduction time and effective refractory period (ERP) of ventricular contractile tissue were measured with right ventricular endocavitary electrodes. Measurements were made with the heart paced at 180 beats/min and without pacing. In group 1 dogs, bupivacaine (plasma level, 2.8 +/- 0.3 microgram/ml) initially caused a prolongation of conduction time and QRS duration, which were further lengthened (approximately doubled) by a temperature decrease of 4 degrees C from baseline. The QT interval and ERP also were increased but to a lesser degree. In dogs in which the effects were most pronounced, rhythm disorders, such as wave burst arrhythmias (most common), premature systoles, ventricular tachycardia, and even ventricular fibrillation, occurred either spontaneously or during pacing. Bupivacaine alone (group 2) increased QRS duration and conduction time significantly, whereas hypothermia alone (Group 3) did not cause changes in any conduction variables. In neither group were dysrhythmias observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity

BACKGROUND AND OBJECTIVES: We previously demonstrated in rats that intravenous infusion of a lipid emulsion increases survival in resuscitation from severe bupivacaine cardiac toxicity. The present studies were undertaken to determine if this method is similarly effective in a non-rodent model using a larger animal. METHODS: Bupivacaine, 10 mg/kg, was administered intravenously over 10 seconds to fasted dogs under isoflurane general anesthesia. Resuscitation included 10 minutes of internal cardiac massage followed with either saline or 20% lipid infusion, administered as a 4-mL/kg bolus followed by continuous infusion at 0.5 mL/kg/min for 10 minutes. Electrocardiogram (EKG), arterial blood pressure (BP), and myocardial pH (pHm) and pO2 (pmO2) were continuously measured. RESULTS: Survival after 10 minutes of unsuccessful cardiac massage was successful for all lipid-treated dogs (n = 6), but with no survivors in the saline controls (n = 6) (P <.01). Hemodynamics, PmO2, and pHm were improved during resuscitation with lipid compared with saline treatment in which dogs did not recover. CONCLUSIONS: We found that infusing a lipid emulsion during resuscitation from bupivacaine-induced cardiac toxicity substantially improved hemodynamics, pmO2, and pHm and increased survival in dogs.     

Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism.

Ventricular fibrillation is frequently induced during cardiac surgery to quiet the operative field. The reported effects of fibrillation on the myocardium vary considerably. In an attempt to better define these effects, we subjected 28 dogs to one hour of total normothermic bypass. Myocardial blood flow, lactate, adenosine triphosphate (ATP), oxygen consumption, and left ventricular fibrillation was induced in 5 dogs and continuous electrical fibrillation in 7 dogs. These groups were compared to two respective control groups with beating hearts of 8 animals each. Coronary sinus flow, total coronary blood flow, left ventricular flow, myocardial oxygen consumption, and myocardial tissue lactate increased significantly in the fibrillating hearts. Left ventricular dp/dt decreased with fibrillation, but not significantly. It is concluded that the metabolic demands of ventricular fibrillation exceed the increase in coronary blood flow, when compared to demands of the beating heart, and that decreased left ventricular performance may result.     

Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine

It is unclear whether the mechanism of death from local anesthetic (LA) intoxication is primarily a consequence of cardiac arrhythmias or myocardial contractile depression, and whether LAs might differ in this susceptibility to these two mechanisms. By using programmable electrical stimulation (PES) protocols in anesthetized, ventilated dogs, we compared the arrhythmogenic potential of bupivacaine (BUP), ropivacaine (ROP), levobupivacaine (LBUP), and lidocaine (LIDO). Open-chest dogs were randomized to receive escalating incremental infusions of the four local anesthetics until cardiovascular collapse. We assumed a concentration relationship of 4:1 for LIDO/BUP, LBUP, and ROP. The effective refractory period did not change significantly until the dose increment corresponding to target concentrations of 8 and 32 microg/mL for BUP, LBUP, ROP, and LIDO, respectively. Thirty percent to 50% increases in effective refractory period occurred in surviving dogs at this dose. The incidence of spontaneous or PES-induced ventricular tachycardia and ventricular fibrillation did not differ among groups. Compared with LIDO, the incidence of PES-induced extrasystoles was more frequent for BUP- and LBUP-treated dogs (P: < 0.05). ROP-treated dogs did not differ from LIDO-treated dogs with respect to PES-induced extrasystoles. At the dose increment preceding cardiovascular collapse, all LAs produced significant increases in heart rate and reductions in blood pressure compared with their respective baseline values. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with BUP does not differ from the incidence that occurs with the single S:(-) enantiomers LBUP and ROP, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity. Implications: Progressive bupivacaine intoxication in anesthetized, ventilated dogs does not produce early arrhythmogenic events. The incidence of programmable electrical stimulation-induced ventricular tachycardia and fibrillation with bupivacaine does not differ from the incidence that occurs with the single S:(-) enantiomers levobupivacaine and ropivacaine, providing further evidence against stereoselective arrhythmogenesis as a primary component of local anesthetic-induced cardiotoxicity.     

Enhancement by ischemia of the risk of cardiac disorders,especially fibrillation,in regional anesthesia with bupivacaine

The impairment of intraventricular conduction by bupivacaine may result in reentrant arrhythmias including ventricular fibrillation. The concentrations responsible for serious accidents are high (5.0 to 8.0 μg/ml), but likely to be lowered by myocardial ischemia which gives rise to similar disorders. Therefore we did an electrophysiological study of bupivacaine's effects in an ischemic area of the myocardium. Monophasic action potential (MAP) of the ventricular myocardium was recorded in 30 anesthetized, open-chest pigs. Conduction time and effective refractory period were also measured. Data were obtained during short periods (10–15 s) of pacing at 180 beats/min, but ventricular beats remained governed by the sinus node in the intervals. Ischemia was produced by occluding the left anterior descending coronary artery completely but transiently (up to 8 min), not far from its origin. Comparison was made between the effects of bupivacaine i.v. (n = 10), ischemia (n= 10) and both factors (n= 10). Two min after injection of bupivacaine 2.0 mg/kg (plasma levels 2.0–3.0 μg/ml), the duration of MAP was only slightly (7.5–15%) prolonged and its ischemia-induced shortening only slightly attenuated by bupivacaine. At the same time, conduction time was considerably (75–150%) lengthened and its ischemia-induced lengthening enhanced, so that ventricular fibrillation induced by coronary occlusion occurred sooner (about 100 instead of 300 s) in the presence of bupivacaine. Consequently, bupivacaine should be used only with caution in individuals whose myocardium is ischemic or liable to ischemia episodes.     

Continuous percutaneous monitoring of muscle pH and oxygen pressure. A new technique for in vivo use.

Newly developed all solid state catheter oxygen pressure (PO2) and pH electrodes were evaluated in dogs in respiratory acidosis and hemorrhagic shock. The electrodes were inserted into the blood vessels and thigh muscle by a percutaneous puncture technique. In animals with respiratory acidosis, arterial, venous, and intramuscular pH decreased in parallel as arterial carbon dioxide pressure (PCO2) increased. During severe acidosis, arterial and venous PO2 did not change appreciably, but intramuscular PO2 decreased moderately, indicating decreased tissue perfusion. In animals with hemorrhagic shock, intramuscular PO2 decreased in proportion to the blood loss, whereas the reduction in intramuscular pH and blood pressure lagged behind blood loss. A similar finding was observed during reinfusion of shed blood in surviving animals. In the animals that died, intramuscular PO2 AND PH remained low after the reinfusion of all shed blood, although arterial blood pressure did return to base line levels.