Arterial blood gases during cardiac arrest: markers of blood flow in a canine model.

Measures of CO2 have been shown to correlate with coronary perfusion pressure and cardiac output during cardiac arrest. We evaluated arterial pH (pHa) relative to blood flow during cardiac arrest in a canine electromechanical dissociation (EMD) model of cardiac arrest using different resuscitation techniques. Following 15 min of cardiac arrest, 24 mongrel dogs received epinephrine with continued CPR or closed-chest cardiopulmonary bypass. Central arterial blood gases, end-tidal carbon dioxide (PetCO2), coronary perfusion pressure and cardiac output were measured. During CPR, prior to epinephrine or bypass, there was no correlation of pHa, PACO2 and PetCO2, with cardiac output or coronary perfusion pressure. Immediately after instituting the resuscitation techniques, both pHa and PaCO2 showed a significant correlation with cardiac output (pHa; R = -0.78, P less than 0.001 and PaCO2; R = 0.87, P less than 0.001) and with coronary perfusion pressure (pHa; R = -0.75, P less than 0.001 and PaCO2; R = 0.75, P less than 0.001). Eventual survivors (n = 15) had an early significant decrease in pHa, base excess and a significant increase in PaCO2 which was not present in non-survivors (n = 9). Neither pHa nor PaCO2 correlate with blood flow under low flow conditions of CPR. However, with effective circulatory assistance, pHa and PaCO2 reflect systemic blood flow and reperfusion washout.

Effect of propionyl-L-carnitine on experimental myocardial infarction in dogs.

Limitation on infarct size, using propionyl-L-carnitine (Sigma-Tau) by itself and with the calcium entry blocker, tiapamil (Hoffmann-LaRoche), was evaluated in two groups of ten dogs each, during chronic (9 days) myocardial infarction. There were eight dogs that served as the control group. A closed-chest model was used to produce the thrombus by placing a helically shaped copper wire in the LAD by catheter technique, under x-ray visualization. Necrotic tissue in serial transventricular sections were delineated by triphenyltetrazolium chloride and measured by computer technique, using an IBM PC interfaced with a digitizing pad, 9 days following occlusion. The mean total amount of necrosis in the propionyl-L-carnitine (7.4%) and the propionyl-L-carnitine/tiapamil (6.7%) groups were significantly less (p less than .01) than found in the control (14.1%) group, reflecting a difference of 50 and 58%, respectively, between the treated groups and control. A number of significant between-group comparisons (p less than .05 to p less than .001), under the same conditions, were found for various ischemia, hemodynamic, and hematologic variables followed before and at 30, 60, 90, 120, and 180 minutes after occlusion, as well as on the second and ninth day. The results of this study strongly suggest that propionyl-L-carnitine and propionyl-L-carnitine with tiapamil has a protective effect on myocardial function, following thrombotic occlusion of the LAD, as well as limiting the resulting infarct size.

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.

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.

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.

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.

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.

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)

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.