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Biomedical subjects

M G Angelos

Publications and source records attributed to M G Angelos.

At least 19 recordsLinked to original sources
PubMed1995

Epinephrine and high-flow reperfusion after cardiac arrest in a canine model.

STUDY OBJECTIVES: Epinephrine has been used in cardiac arrest to increase the low blood flow generated by standard CPR methods. Reperfusion with high flow such as that obtained with cardiopulmonary bypass (CPB) may obviate the need for or alter the dose of epinephrine after cardiac arrest. The objective of this study was to evaluate the effect of high-flow reperfusion after cardiac arrest with and without epinephrine on coronary perfusion pressure, defibrillation energy, restoration of spontaneous circulation (ROSC), and 2-hour survival after prolonged cardiac arrest. DESIGN: Prospective, randomized, double-blind, placebo-controlled study using a canine model. INTERVENTIONS: Thirty mongrel dogs were randomized to receive, after ventricular fibrillation cardiac arrest of 12 minutes' duration without CPR, placebo (n = 10), standard-dose epinephrine (.02 mg/kg) (n = 10), or high-dose epinephrine (.2 mg/kg) (n = 10) during reperfusion with CPB. Epinephrine or placebo was given with the start of CPB and then every 5 minutes, followed by countershock until ROSC or crossover at the fourth dose to high-dose epinephrine. RESULTS: ROSC was achieved in the first 15 minutes of bypass in 10 of 10 dogs given high-dose epinephrine, in 9 of 10 given standard-dose epinephrine, and in 1 of 10 given placebo. After the crossover to high-dose epinephrine, ROSC was achieved in 8 of 10 dogs originally given placebo and the remaining animal given the standard dose of epinephrine. During early reperfusion, the high-dose group had a higher mean coronary perfusion pressure (high dose, 153 + 62 mm Hg; standard dose, 81 +/- 18 mm Hg; placebo, 51 +/- 15 mm Hg; P < .002) and a shorter mean ROSC time (high dose, 16.2 +/- 8 minutes; standard dose, 20.3 +/- 3.6 minutes; placebo, 27.9 +/- 3.2; P < .02) and required less defibrillation energy. CPB flow during ventricular fibrillation was 63% of baseline cardiac output in all three groups. Two-hour survival was 5 of 10 in the high-dose group, 8 of 10 in the standard-dose group, and 5 of 10 in the placebo group. CONCLUSION: Restoration of high blood flow alone is insufficient to restore spontaneous circulation after prolonged cardiac arrest. Epinephrine, when administered early under high-flow conditions, increases coronary perfusion pressure, decreases defibrillation energy, and decreases time elapsed before ROSC. Higher doses of epinephrine under conditions of high-flow reperfusion do not improve 2-hour survival compared with standard-dose epinephrine.

Animals↗
PubMed1995

Myocardial metabolic changes during reperfusion of ventricular fibrillation: a 31P nuclear magnetic resonance study in swine.

OBJECTIVE: Myocardial metabolic requirements during reperfusion of ventricular fibrillation are poorly understood. The objective of this study was to determine if controlled reperfusion after a clinically relevant global ischemia period of 10 mins was sufficient to prevent or reverse myocardial ischemia as indicated by changes in myocardial high energy phosphates, myocardial intracellular pH, and great cardiac vein lactate. DESIGN: Prospective laboratory study with controlled reperfusion. SETTING: Research laboratory at a university medical center. SUBJECTS: Five swine weighing 19 +/- 3 kg. INTERVENTIONS: Ten minutes of nonperfused ventricular fibrillation followed by reperfusion with cardiopulmonary bypass (flow 30 mL/kg/min) for 50 mins. MEASUREMENTS AND MAIN RESULTS: Myocardial adenosine triphosphate (ATP), phosphocreatine, and intracellular pH were determined using in vivo 31P nuclear magnetic resonance. Myocardial blood flow, measured by 15-mu radiolabeled microspheres, was significantly increased above baseline during reperfusion. Phosphocreatine was depleted during the 10 mins of nonperfused ventricular fibrillation, but recovered to 122 +/- 18% of baseline with reperfusion and was 112 +/- 18% at 60 mins (p < .005). ATP concentrations decreased to 51 +/- 16% of baseline after 10 mins of nonperfused ventricular fibrillation, improved to 67 +/- 9% of baseline with early reperfusion, and were 65 +/- 9% of baseline at 60 mins (p < .02). Myocardial intracellular pH improved from 6.11 +/- 0.18 after 10 mins of nonperfused ventricular fibrillation, to 6.89 +/- 0.20 with early reperfusion, and then decreased to 6.85 +/- 0.35 at 60 mins ventricular fibrillation (p < .001). Despite myocardial blood flows higher than baseline during the reperfusion period, great cardiac vein/aortic lactate gradient increased over the reperfusion period. CONCLUSION: Prolonged reperfusion with supranormal myocardial blood flow does not restore normal myocardial aerobic metabolism in the fibrillating myocardium after a 10-min nonperfused ventricular fibrillation period.

Adenosine Triphosphate↗
PubMed1995

Epinephrine-mediated changes in carbon dioxide tension during reperfusion of ventricular fibrillation in a canine model.

OBJECTIVE: Previous studies suggest that epinephrine may alter the correlation of perfusion with measures of PCO2 during cardiopulmonary resuscitation. This study investigated the effects of epinephrine on PaCO2 and mixed venous PCO2 in a high-flow reperfusion model of cardiac arrest. DESIGN: Prospective, block randomized, blinded, placebo-controlled, laboratory study. SUBJECTS: Thirty mixed breed canines. INTERVENTIONS: After a 12-min ventricular fibrillation cardiac arrest, 30 mixed breed canines were reperfused with standardized (3200 revolutions/min) cardiopulmonary bypass and were given placebo (n = 10), standard dose epinephrine (0.02 mg/kg; n = 10), or high-dose epinephrine (0.2 mg/kg; n = 10). Arterial and mixed venous blood gases, coronary perfusion pressure, pump flow and peripheral vascular resistance were compared between groups during the early reperfusion period using analysis of variance with a post hoc Tukey's multiple comparison test. MEASUREMENTS AND MAIN RESULTS: Baseline variables were similar between groups. With reperfusion, the high-dose epinephrine group had higher coronary perfusion pressures (p < .002), lower systemic pump flow (p < .01), and higher peripheral vascular resistance (p < .001). In the high-dose epinephrine group, both PaCO2 (high-dose epinephrine, 40 +/- 6 torr [5.3 +/- 0.8 kPa]; standard dose epinephrine, 45 +/- 7 torr [6.0 +/- 0.9 kPa]; placebo, 54 +/- 4 torr [7.2 +/- 0.5 kPa]; p < .01) and mixed venous PCO2 (high-dose epinephrine, 55 +/- 10 torr [7.3 +/- 1.3 kPa]; standard dose epinephrine, 57 +/- 9 torr [7.6 +/- 1.2 kPa]; placebo, 67 +/- 4 torr [8.9 +/- 0.5 kPa]; p < .05) were significantly decreased, and arterial pH, PaO2, and mixed venous PO2 were significantly increased compared with the placebo group. CONCLUSION: In this model, when ventilation and CO2 production are constant, the decrease in PaCO2 with epinephrine is due to decreased pulmonary blood flow (flow to membrane oxygenator) and peripheral shunting.

Animals↗
PubMed1994

Organ blood flow following cardiac arrest in a swine low-flow cardiopulmonary bypass model.

STUDY OBJECTIVE: To determine organ blood flow changes, relative to baseline, following cardiac arrest and resuscitation in a closed-chest cardiac arrest swine model using cardiopulmonary bypass to achieve reproducible return of spontaneous circulation (ROSC). INTERVENTIONS: Following 10 min of ventricular fibrillation (VF), animals (n = 10) received low-flow cardiopulmonary bypass at 10 ml/kg/min from 10-15 min. At 15 min of VF, norepinephrine (0.12 mg/kg) was given and bypass flow increased to 50 ml/kg/min, followed by countershocks at 16 min. Following ROSC, cardiopulmonary bypass was immediately weaned off with norepinephrine support. Organ blood flows were determined during normal sinus rhythm, during reperfusion of VF and during the early post-ROSC period while off cardiopulmonary bypass support. Organ blood flows during the early ROSC period were compared with organ blood flow at baseline and during VF. RESULTS: During early reperfusion of VF prior to any drug therapy, myocardial, cerebral and abdominal organ blood flows were all low. All animals achieved ROSC at 16.9 +/- 0.7 min and were weaned from bypass in < 5 min following ROSC. During the early post-ROSC period, blood flow to the myocardial, cerebral and adrenal vascular beds was significantly elevated relative to baseline. Simultaneously, blood flow to the kidneys, liver, spleen and lungs was reduced relative to baseline. CONCLUSIONS: This low-flow bypass model produces reproducible high resuscitation rates and ROSC times. Early post-resuscitation organ blood flow is characterized by a selective hyperemia involving the cerebral, myocardial and adrenal vascular beds, in contrast to hypoperfusion of the pulmonary and mesenteric vascular beds.

Animals↗
PubMed1994

Norepinephrine-induced hypertension following cardiac arrest: effects on myocardial oxygen use in a swine model.

STUDY OBJECTIVE: Recent studies suggest that norepinephrine-induced hypertension early after cardiac arrest ameliorates cerebral hypoperfusion and improves neurologic outcome. The purpose of this study was to evaluate the effects of early norepinephrine-induced hypertension on postresuscitation myocardial blood flow and oxygen use. DESIGN: Prospective, controlled laboratory study. PARTICIPANTS: Ten swine. INTERVENTIONS: All animals underwent 10 minutes of ventricular fibrillation cardiac arrest followed by 5 minutes of low-flow cardiopulmonary bypass (10 mL/kg.min), norepinephrine (0.12 mg/kg), and defibrillation. Animals then were assigned to a hypertension group (mean aortic pressure, 95 mm Hg) or a control group (mean aortic pressure, 75 mm Hg) by titrating a norepinephrine infusion to attain the prescribed aortic pressure. RESULTS: Myocardial blood flow, perfusion pressure, and oxygen metabolism were compared between groups at different times using analysis of variance with a post-hoc Tukey test. Groups had similar myocardial blood flow during ventricular fibrillation, total defibrillation energy, and time to restoration of spontaneous circulation. Fifteen minutes after restoration of spontaneous circulation, the hypertension group had significantly elevated myocardial blood flow, 965 +/- 314 mL/min.100 g versus 325 +/- 67 mL/min.100 g in the control group (P < .001), myocardial oxygen consumption of 51.2 +/- 26.9 mL O2/min.100 g versus 6.4 +/- 3.4 mL O2/min.100 g (P < .001), and myocardial oxygen extraction of 46% +/- 20% versus 14% +/- 4% (P < .01). CONCLUSION: In the early resuscitation period, increasing the norepinephrine dose to induce mild hypertension significantly increases oxygen use in the postischemic myocardium.

Analysis of Variance↗
PubMed1993

Fructose-1,6-diphosphate fails to limit early myocardial infarction size in a canine model.

STUDY OBJECTIVE: Fructose-1,6-diphosphate (FDP) appears to improve early post-myocardial infarction hemodynamics and limit early myocardial infarct size in previous canine studies. However, these studies did not account for the effect of collateral blood flow on infarct size. Our objective was to determine the effect of FDP on early infarct size and hemodynamics while measuring regional myocardial blood flow. DESIGN: A prospective, blinded, placebo-controlled laboratory study using a canine open-chest left anterior descending coronary artery (LAD) occlusion model. INTERVENTIONS: Twenty-two mongrel dogs were assigned randomly to receive either FDP (175 mg/kg, then 2 mg/kg/min for two hours) or placebo, beginning five minutes after LAD occlusion. MEASUREMENTS AND MAIN RESULTS: Regional myocardial blood flow, hemodynamics, and myocardial infarct size were determined. Infarct size was assessed using magnetic resonance imaging in a subset of animals. Three of the 22 dogs had no infarct and significantly higher collateral blood flow than the 19 animals with myocardial infarction (P < .001). Four hours after LAD occlusion, cardiac index, dP/dtmax, heart rate, and systolic and mean aortic pressures were not statistically different between groups. Infarct size expressed as area of necrosis/area at risk was similar between groups (FDP, 0.55 +/- 0.28; controls, 0.59 +/- 0.31). CONCLUSION: FDP given after occlusion of the LAD in this canine model did not limit early myocardial infarct size.

Animals↗
PubMed1993

Early detection of myocardial infarction with magnetic resonance imaging in a canine model.

STUDY OBJECTIVE: To determine the effectiveness of magnetic resonance imaging in detecting early myocardial infarction in vivo after coronary artery occlusion. DESIGN: A prospective, controlled canine study using a left anterior descending coronary artery ligation model. INTERVENTIONS: After thiopental anesthesia, nine mongrel dogs underwent cardiac-gated magnetic resonance imaging with a 2.35-T magnet with a 40-cm bore before and four hours after ligation of the left anterior descending coronary artery. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and left ventricular blood flow changes were determined. The mean image intensity ratio of the suspected infarct region to the normal myocardium was determined in the four-hour postocclusion images and compared with the ratio from the same anatomic region obtained at baseline. The area of necrotic and ischemic myocardium was determined using fluorescein and triphenyl tetrazolium chloride staining immediately after four-hour images. All animals were noted to have necrotic (range, 1.8% to 20.4% of ventricles) and ischemic (range, 9.2% to 36.6% of ventricles) myocardium with histochemical staining. The mean intensity ratio of infarcted myocardium four hours after left anterior descending coronary artery occlusion was significantly higher than baseline (four hours, 2.31 +/- 0.82; baseline, 1.02 +/- 0.09; P < .002). CONCLUSION: Magnetic resonance imaging can distinguish myocardial edema associated with acute infarcting myocardium in vivo as early as four hours after left anterior descending coronary artery occlusion. Magnetic resonance imaging may be clinically useful in identifying thrombolytic therapy candidates among acute myocardial infarction patients presenting with atypical symptoms.

Animals↗
PubMed1992

Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation.

STUDY OBJECTIVE: To determine the effects of cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post-countershock electromechanical dissociation. DESIGN: Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies. INTERVENTIONS: After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard-dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard-dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). CONCLUSION: Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation.

Animals↗
PubMed1992

Arterial pH and carbon dioxide tension as indicators of tissue perfusion during cardiac arrest in a canine model.

BACKGROUND AND METHODS: Previous studies have shown that Paco2 and end-tidal CO2 reflect coronary artery perfusion pressures during cardiac arrest. We investigated the relationship of coronary artery perfusion pressure to central arterial pH and Paco2 values during resuscitation from cardiac arrest in a canine model. Twenty-four mongrel dogs were block randomized to three different resuscitation groups after induction of ventricular fibrillation and cardiac arrest: a) standard cardiopulmonary resuscitation (CPR) and advanced life support (n = 8); b) cardiopulmonary bypass (n = 8); or c) open-chest CPR (n = 8). Central arterial blood gases and perfusion pressures were monitored during cardiac arrest and during resuscitation. RESULTS: Prearrest blood gases and hemodynamic values were similar between groups. Sixteen dogs from all three groups were successfully resuscitated. Survivors had significantly higher coronary artery perfusion pressure (p = .03), Paco2 (p = .015), and lower pH (p = .01) values than nonsurvivors. There was no correlation of pH and Paco2 during mechanical external CPR. However, after institution of the different resuscitation techniques, pH and Paco2 each showed a statistically significant correlation (r2 = .50 and .33, respectively) with coronary artery perfusion pressure. CONCLUSIONS: Central arterial pH and Paco2 monitoring during cardiac arrest may reflect the adequacy of tissue perfusion during resuscitation and may predict resuscitation outcome from ventricular fibrillation.

Animals↗
PubMed1991

Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model.

STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB.

Animals↗
PubMed1990

Improved survival and reduced myocardial necrosis with cardiopulmonary bypass reperfusion in a canine model of coronary occlusion and cardiac arrest.

STUDY QUESTION: Does cardiopulmonary bypass (CPB) improve resuscitation rates and limit infarct size after cardiac arrest and acute myocardial infarction? DESIGN: Controlled randomized trial with all animals undergoing left anterior descending coronary artery occlusion and subsequent ventricular fibrillation and resuscitation. All animals were supported for four hours after resuscitation in an intensive care setting. INTERVENTION: Group 1 (eight) was resuscitated with standard external CPR and advanced life support. Group 2 (eight) was resuscitated with CPB. MEASUREMENTS AND MAIN RESULTS: Group hemodynamic, resuscitation variables, number resuscitated, and number of four-hour survivors were compared. Ischemic and necrotic myocardial weights were determined with histochemical staining techniques in four-hour survivors. Infarct size was measured as the ratio of necrotic weight to ischemic weight. Significantly fewer dogs were resuscitated in group 1 (four of eight) than in group 2 (eight of eight) (P less than .05). Group 2 survivors required significantly less epinephrine and lidocaine than group 1 survivors (P less than .05) and higher aortic diastolic and coronary perfusion pressures after CPB (P less than .001). The ratio of myocardial necrotic weight to ischemic weight at four hours was 0.82 +/- 0.25 in group 1 and 0.22 +/- 0.25 in group 2 (P less than .05). However, collateral blood flow was not measured in this study. CONCLUSION: This pilot study further substantiates the improvement in resuscitation rates obtainable with CPB. CPB may also limit infarct size during the postresuscitation period and requires further study.

Animals↗
PubMed1990

Cardiopulmonary bypass in a model of acute myocardial infarction and cardiac arrest.

Cardiopulmonary bypass (CPB) reperfusion has demonstrated improved resuscitation rates in ventricular fibrillation cardiac arrest models. To investigate the effectiveness of CPB reperfusion in an ischemic cardiac arrest setting, simulating the clinical scenario of myocardial ischemia preceding sudden cardiac death, we developed a canine model of acute myocardial infarction followed by ventricular fibrillation. Sixteen dogs were randomly assigned to two groups. Group 1 (eight) had ventricular fibrillation induced without left anterior descending coronary artery occlusion. Group 2 (eight) had a thrombogenic copper coil placed in the left anterior descending artery and showed ECG evidence of acute myocardial infarction before induction of ventricular fibrillation. CPR commenced after eight minutes of ventricular fibrillation. Epinephrine 0.05 mg/kg and NaHCO3 1.0 mEq/kg were administered at ten minutes. CPB was begun at 12 minutes and continued for one hour. Myocardial ischemic and necrotic areas were determined in four-hour survivors by dual histochemical staining. All animals were resuscitated; all eight group 1 and six of eight group 2 animals survived to four hours. With the onset of CPB, coronary perfusion pressures increased significantly by 68.6 +/- 31.8 (SD) mm Hg in group 1 and 56.2 +/- 34.6 mm Hg in group 2 over those obtained with CPR (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Nonsteroidal anti-inflammatory drugs and coma: a case report of fenoprofen overdose.

We present the case of a 17-year-old girl who ingested 24 to 36 g fenoprofen as a suicidal gesture. She presented with coma, hypotension, metabolic acidosis, and respiratory depression within four hours of ingestion. The most common adverse effects of the nonsteroidal anti-inflammatory drugs occur in both therapeutic and toxic doses and include gastrointestinal upset, blood dyscrasias, and analgesic nephropathy. The propionic acid derivatives of nonsteroidal anti-inflammatory drugs, including fenoprofen and ibuprofen, are rarely associated with severe toxic effects. This is the first report of pure fenoprofen overdose presenting as coma and metabolic acidosis.

Acidosis↗
PubMed1986

Needle emboli to lung following intravenous drug abuse.

Presented is the case of a 36-year-old man using central venous sites for injection of street drugs. X-ray study revealed numerous retained subcutaneous needles as well as a needle that had embolized to the lung periphery. This represents, to the best of our knowledge, a previously unreported complication of central venous injection of street drugs.

Adult↗