Higher Coronary Perfusion Pressure Research Articles

Time-Dependent Association Between Agonal Respirations and Cardiopulmonary Resuscitation Hemodynamics in a Porcine Model of Cardiac Arrest

Objective: Agonal respirations (AR) are common in patients with cardiac arrest (CA) and are associated with a higher likelihood of successful return of spontaneous circulation (ROSC). Prior preclinical studies suggest that the favorable effects of AR may be mediated by improved coronary perfusion pressure (CPP) during subsequent cardiopulmonary resuscitation (CPR) efforts, but whether this relationship is influenced by the duration of CA has yet to be studied. Accordingly, we measured CPR hemodynamics in swine following 7 minutes or 10 minutes of untreated ventricular fibrillation (VF) to determine if the frequency of AR is associated with CPP after prolonged CA. Methods: Swine (n=71) were subjected to either 7 minutes (n=50) or 10 minutes (n=21) of electrically-induced VF CA, during which the frequency of AR was recorded before the initiation of CPR with chest compressions (100/minute) and mechanical ventilation (16-20 breaths/minute). CPP was assessed during CPR by calculating the difference between aortic pressure and right atrial pressure during decompression. Animals were retrospectively stratified into two groups (high and low frequency of AR) based on the median number of AR in each cohort (7-minute CA median = 6 AR; 10-minute CA median = 9 AR).>Results: In the 7-minute CA cohort, the high AR group (9.7±2.9 AR; n=28) had a significantly longer time from first to last AR (102±6 vs. 34±6 seconds; p<0.001), shorter time from final AR to CPR initiation (208±8 vs. 280±15 seconds; p<0.001), and higher CPP during CPR (14.4±1.0 vs. 9.3±0.6 mmHg; p<0.001) than the low AR group (2.9±0.4 AR; n=22). In contrast, following 10 minutes of CA, the high AR group (12.0±0.4 AR; n=11) did not have a significantly different CPP during CPR (8.7±1.8 vs. 10.4±1.5 mmHg; p=0.48) when compared to the low AR group (6.2±0.5 AR; n=10). A greater number of defibrillation attempts were required to terminate VF after 10 minutes of CA (3.0±0.6) vs. 7 minutes of CA (1.2±0.1; p<0.001), but this was not impacted by the frequency of AR in either cohort. Conclusion: Consistent with prior studies in swine subjected to 5 minutes of untreated CA, a high frequency of AR during a 7-minute episode of CA was associated with higher CPP upon initiation of CPR. However, the favorable effects of AR frequency on CPP during CPR were no longer apparent when the duration of untreated CA was extended to 10 minutes. These results demonstrate that the beneficial effects of AR on CPR hemodynamics are time-dependent and highlight the importance of early initiation of CPR following CA. Supported by funding from the NIH and US Department of Veteran's Affairs. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 299: Effect of Start Position and Compression Depth on Mechanical CPR Hemodynamics in Swine

Introduction: Mechanical devices offer the ability to provide consistent fixed-depth chest compressions during CPR. Although compression depth is considered a primary determinant of CPR quality, the influence of other device settings has received less attention. Accordingly, we evaluated the combined effect of compression depth and device start position on CPR hemodynamics in a porcine model of cardiac arrest (CA). Methods: Swine (n=119) were subjected to 7-10 min of CA following electrical induction of ventricular fibrillation. CPR was subsequently performed manually (target peak aortic pressure: 100 mmHg; n=73) or with a mechanical compression system (LUCAS 3.1, Stryker; n=46). Within the mechanical CPR group, animals received 102 compressions/min using either factory default settings (“QuickFit” automated suction cup start position; compression depth: 2.1”; n=13) or custom settings (manual suction cup start position; compression depth: 1.8”; n=33). Aortic pressure (Ao), coronary perfusion pressure (CPP), and regional cerebral oxygen saturation (rSO 2 ; via near infrared spectroscopy) were compared between groups after 1 min of CPR. Results: Mechanical CPR with automated suction cup start position and compression depth of 2.1” resulted in significantly higher peak Ao and CPP than mechanical CPR with manual start position and compression depth of 1.8” ( Table ). Compared with manual CPR, only mechanical CPR with automated start position and compression depth of 2.1” led to a higher CPP. However, cerebral rSO 2 values fell from 61±1 % at baseline to 49±1 % during CA (p<0.01) and did not increase during CPR in any group. Conclusion: Compared with a manual start position and compression depth of 1.8”, use of the LUCAS “QuickFit” feature and compression depth of 2.1” led to a significantly higher CPP during mechanical CPR. Future studies are necessary to determine if differences persist during prolonged CPR with and without concomitant vasopressor administration.

Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model.

Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline. After 5min of VF, 20 pigs randomly received either pralidoxime (40mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes. All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2. Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

Abstract 359: Use of Resuscitative Balloon Occlusion of the Aorta in a Swine Model of Prolonged Cardiac Arrest

Introduction: Despite advancements in CPR, survival to hospital discharge remains low for in- and out-of-hospital cardiac arrest (CA). Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an evolving tool for temporary control of non-compressible truncal hemorrhage. In this investigation, we examined whether REBOA use during non-traumatic CA would produce favorable hemodynamic changes associated with return of spontaneous circulation (ROSC). Hypothesis: We hypothesized that REBOA use during CPR would result in higher coronary perfusion pressure (CPP) and common carotid artery blood flow (C-Flow) in a prolonged model of CA. Methods: Six male swine were anesthetized and instrumented to measure and monitor CPP, and C-Flow. A REBOA catheter (Prytime Medical Devices) was advanced into zone 1 of the aorta through the femoral artery. Ventricular fibrillation was electrically induced and untreated for 8 minutes. CPR was started manually at minute-8, then changed to mechanical CPR at minute-12 for the duration of the experiment. Continuous infusion of epinephrine (0.0024mg/kg/min) was simultaneously started with mechanical CPR. The REBOA balloon was inflated beginning at minute-16 for 3 minutes then deflated for 3 minutes for a total of 6 cycles. At the end of the final cycle (REBOA inflation), CPR was stopped (after 33 minutes of total arrest time) and animals were defibrillated using 200 J biphasic shocks, repeated up to 6 times. Animals achieving ROSC were monitored for an additional 25 minutes. Results: Analysis using repeated measure ANOVA showed significant differences between balloon deflation and inflation periods for CPP (p<0.0001) with mean difference(SD) of 14(2.6) (Range: 17 to 42) mmHg and for C-Flow (p<0.0001) with mean difference(SD) 16(23) (Range: 115 to 269) mL/min across all animals. Three animals achieved ROSC and had significantly higher CPP (48 vs. 24mmHg, p<0.0001) and C-Flow (249 vs. 168mL/min) by t-test (p<0.0001). Post-mortem aortic histology did not reveal any changes produced by balloon inflation. Conclusion: REBOA significantly increased CPP and C-Flow in this swine model of prolonged CA. These increases may have contributed to the ability to achieve ROSC after greater than 30 min of CA.

Pulmonary Vasodilator Therapy in Shock-associated Cardiac Arrest.

Many in-hospital cardiac arrests are precipitated by hypotension, often associated with systemic inflammation. These patients are less likely to be successfully resuscitated, and novel approaches to their treatment are needed. To determine if the addition of inhaled nitric oxide (iNO) to hemodynamic-directed cardiopulmonary resuscitation (HD-CPR) would improve short-term survival from cardiac arrest associated with shock and systemic inflammation. In 3-month-old swine (n = 21), LPS was intravenously infused, inducing systemic hypotension. Ventricular fibrillation was induced, and animals were randomized to blinded treatment with either: 1) HD-CPR with iNO, or 2) HD-CPR without iNO. During HD-CPR, chest compression depth was titrated to peak aortic compression pressure of 100 mm Hg, and vasopressor administration was titrated to coronary perfusion pressure greater than or equal to 20 mm Hg. Defibrillation attempts began after 10 minutes of resuscitation. The primary outcome was 45-minute survival. The iNO group had higher rates of 45-minute survival (10 of 10 vs. 3 of 11; P = 0.001). During cardiopulmonary resuscitation, the iNO group had lower pulmonary artery relaxation pressure (mean ± SEM, 10.9 ± 2.4 vs. 18.4 ± 2.4 mm Hg; P = 0.03), higher coronary perfusion pressure (21.1 ± 1.5 vs. 16.9 ± 1.0 mm Hg; P = 0.005), and higher aortic relaxation pressure (36.6 ± 1.6 vs. 30.4 ± 1.1 mm Hg; P < 0.001) despite shallower chest compressions (5.88 ± 0.25 vs. 6.46 ± 0.40 cm; P = 0.02) and fewer vasopressor doses in the first 10 minutes (median, 4 [interquartile range, 3-4] vs. 5 [interquartile range, 5-6], P = 0.03). The addition of iNO to HD-CPR in LPS-induced shock-associated cardiac arrest improved short-term survival and intraarrest hemodynamics.

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest*

To assess the effectiveness of sodium nitroprusside (SNP)-"enhanced" cardiopulmonary resuscitation (SNPeCPR) on 24-hr survival rates compared to standard CPR in animals after cardiac arrest. SNPeCPR consists of large intravenous SNP bolus doses during CPR enhanced by active compression-decompression CPR, an inspiratory impedance threshold device (ITD), and abdominal binding (AB). The combination of active compression-decompression CPR+ITD+AB without SNP will be called "enhanced" or eCPR. Randomized, blinded, animal study. Preclinical animal laboratory. Twenty-four female farm pigs (30 ± 1 kg). Isoflurane anesthetized and intubated pigs were randomized after 8 mins of untreated ventricular fibrillation to receive either standard CPR (n = 8), SNPeCPR (n = 8), or eCPR (n = 8) for 25 mins followed by defibrillation. The primary end point was carotid blood flow during CPR and 24-hr survival with good neurologic function defined as an overall performance category score of ≤2 (1 = normal, 5 = brain dead or dead). Secondary end points included hemodynamics and end-tidal CO2. SNPeCPR significantly improved carotid blood flow and 24-hr survival rates with good neurologic function compared to standard CPR or eCPR (six of eight vs. zero of eight vs. one of eight, p < .05). The improved survival rates were associated with higher coronary perfusion pressure and ETco2 during CPR. In pigs, SNPeCPR significantly improved hemodynamics, resuscitation rates, and 24-hr survival rates with good neurologic function after cardiac arrest when compared with standard CPR or eCPR alone.

The effects of vitamin C and nitric oxide synthase inhibition on coronary flow and oxidative stress markers in isolated rat heart

The aim of this study was to assess the effects of vitamin C (ascorbic acid) on coronary flow and oxidative stress markers with or without non-specific inhibition of nitric oxide synthase by N(ω)-nitro-L-arginine monomethyl ester (L-NAME) in isolated rat hearts. The hearts of male Wistar albino rats (n = 12, age 8 weeks, body mass 180-200 g) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure (40-120 cm H2O). Coronary flow, nitrite outflow, superoxide anion production, and index of lipid peroxidation (by measuring thiobarbituric acid reactive substances) in coronary effluent were determined. The experiments were performed during control conditions and in presence of vitamin C (100 µM) alone or vitamin C (100 µM) + L-NAME (30 µM). Administration of vitamin C induced only increase of nitrite levels, while vitamin C + L-NAME induced significant decrease of coronary flow above autoregulatory range, i.e. especially at higher coronary perfusion pressure (CPP) values, accompanied with similar dynamic in nitrite outflow. Vitamin C + L-NAME also induced significant decrease in TBARS production. The results of our study show no significant effects of vitamin C administration either on ROS levels or on coronary flow in isolated rat heart.

Myocardial Infarction in Coronary Bypass Surgery Using On-Pump, Beating Heart Technique with Pressure-and Volume-Controlled Coronary Perfusion

Even with the current aerobic techniques in myocardial protection, perioperative myocardial infarction can still occur. In this study, we sought to find out whether there is a method-specific mechanism of ischemic injury in coronary bypass surgery using an on-pump beating heart technique. For this reason, we investigated localization and the extent of myocardial infarction in correlation to the severity of coronary artery stenosis. We discuss strategies for reduction of infarction incidence. 34 patients, who after isolated coronary bypass procedure developed non-Q or Q wave infarction were selected for the study. In 12 of 34 patients (group A) beating heart technique and in 22 of 34 patients (group B) cardioplegic arrest was used for myocardial protection. The study was conducted retrospectively and included patients with stable, unstable, and postinfarction angina without preoperative enzymatic evidence of ischemic injury and with technically noncomplicated coronary bypass grafting. Excluded from the study were emergency and redo procedures. In group A, in all instances, the left anterior descending artery was grafted as the last vessel and while distal anastomoses were constructed, coronary perfusion was maintained by using a perfusion catheter. Most patients in both groups had triple-vessel disease (10 of 12 patients group A; 17 of 22 patients group B), all patients received complete revascularization; 7 of 12 patients in group A and 5 of 22 patients in group B had significant or critical left main stem stenosis. In group A, 11 infarctions occurred in LAD-(12 stenotic), 1 in CX-(11 stenotic), and 1 in RCA-(11 stenotic) supply area, four were Q wave infarctions. In group B, eight infarctions occurred in LAD (22 stenotic), four in CX (17 stenotic), and 14 in RCA (20 stenotic) supply area, eight were Q wave infarctions. In group A, the infarction incidence in the LAD area was 10-times higher than in CX and RCA areas. In group B, the infarction incidence in the RCA area was 2- and 3-times higher than in the LAD and CX areas, respectively. In both groups no correlation between infarction incidence and severity of stenosis was observed. Using an on-pump beating heart technique, higher coronary perfusion pressures, avoidance of extreme upward retraction of the heart during revascularization of the CX-branch, as well as choosing the revascularization of the LAD as the first vessel, could possibly contribute to better myocardial protection. In hearts arrested with cardioplegic solution, the right ventricle is probably more susceptible to ischemic injury, especially when RCA is poorly collateralized. For adequate protection, choosing the revascularization of the RCA as the first vessel with immediate repeated cardioplegia via a RCA graft, higher perfusion pressures and antegrade with retrograde cardioplegia delivery, may be advantageous.

Abstract P115: Higher Threshold and Dose of Coronary Perfusion Pressure are Associated with ROSC in Prolonged Swine Cardiac Arrest

Introduction: The amount of myocardial perfusion required for successful defibrillation after prolonged cardiac arrest is not known. Coronary perfusion pressure (CPP) is a surrogate for myocardial perfusion. One limited clinical study reported that a threshold of 15mmHg was necessary for return of spontaneous circulation (ROSC), and that CPP was predictive of ROSC. A distinction between threshold and dose of CPP has not been reported. Hypothesis: Animals that achieve ROSC will have higher mean CPP and higher area under the CPP curve (AUC) than no-ROSC swine. Methods: Data from 4 similar swine cardiac arrest studies were retrospectively pooled. Animals had undergone 8 –11 minutes of untreated ventricular fibrillation, 2 minutes of mechanical CPR, administration of drugs, and 3 more minutes of CPR prior to the first shock. Mean CPP ± standard error was derived from the last 20 compressions of each 30 second epoch of CPR and compared between ROSC/no-ROSC groups by RM-ANOVA. AUC for all compressions delivered over the 5 minutes was calculated by direct summation and compared by Kruskal-Wallis test. Prediction of ROSC was assessed by logistic regression. Results : During 5 minutes of CPR (n=80), mean CPP ± SEM was higher in animals with ROSC (n=63) (p &lt; 0.001). Animals with ROSC received more total flow than animals without ROSC (p &lt; 0.001). Two regression models identified CPP (OR 1.11; 95% CI 1.05, 1.18) and AUC (OR 1.10; 95% CI 1.05, 1.16) as predictors of ROSC. Experimental protocol also predicted ROSC in each model (OR 1.70; 95% CI 1.15, 2.50) and (OR 1.59; 95% CI 1.12, 2.25), respectively. Conclusion : Higher CPP threshold and dose are associated with and predictive of ROSC.

Use of mathematic modeling to compare and predict hemodynamic effects of the modified Blalock–Taussig and right ventricle–pulmonary artery shunts for hypoplastic left heart syndrome

Stage one reconstruction (Norwood operation) for hypoplastic left heart syndrome can be performed with either a modified Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. Both methods have certain inherent characteristics. It is postulated that mathematic modeling could help elucidate these differences. Three-dimensional computer models of the Blalock-Taussig shunt and right ventricle-pulmonary artery shunt modifications of the Norwood operation were developed by using the finite volume method. Conduits of 3, 3.5, and 4 mm were used in the Blalock-Taussig shunt model, whereas conduits of 4, 5, and 6 mm were used in the right ventricle-pulmonary artery shunt model. The hydraulic nets (lumped resistances, compliances, inertances, and elastances) were identical in the 2 models. A multiscale approach was adopted to couple the 3-dimensional models with the circulation net. Computer simulations were compared with postoperative catheterization data. Good correlation was found between predicted and observed data. For the right ventricle-pulmonary artery shunt modification, there was higher aortic diastolic pressure, decreased pulmonary artery pressure, lower Qp/Qs ratio, and higher coronary perfusion pressure. Mathematic modeling predicted minimal regurgitant flow in the right ventricle-pulmonary artery shunt model, which correlated with postoperative Doppler measurements. The right ventricle-pulmonary artery shunt demonstrated lower stroke work and a higher mechanical efficiency (stroke work/total mechanical energy). The close correlation between predicted and observed data supports the use of mathematic modeling in the design and assessment of surgical procedures. The potentially damaging effects of a systemic ventriculotomy in the right ventricle-pulmonary artery shunt modification of the Norwood operation have not been analyzed.

A Comparison of the Combination of Epinephrine and Vasopressin with Lipid Emulsion in a Porcine Model of Asphyxial Cardiac Arrest After Intravenous Injection of Bupivacaine

In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine-induced cardiac arrest. After administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 2 +/- 0.5 (mean +/- SD) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment. In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine. In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.

Multiscale modelling in biofluidynamics: Application to reconstructive paediatric cardiac surgery

Multiscale computing is a challenging area even in biomechanics. Application of such a methodology to quantitatively compare postoperative hemodynamics in congenital heart diseases is very promising. In the treatment of hypoplastic left heart syndrome, which is a congenital heart disease where the left ventricle is missing or very small, the necessity to feed the pulmonary and systemic circulations is obtained with an interposition shunt. Two main options are available and differ from the sites of anastomoses: (i) the systemic-to-pulmonary conduit (Blalock–Taussig shunt known as the Norwood Operation (NO)) connecting the innominate artery (NO-BT) or the aorta (NO-CS) to the right pulmonary artery and (ii) the right ventricle to pulmonary artery shunt (known as Sano operation (SO)). The proposition that the SO is superior to the NO remains controversial. 3-D computer models of the NO (NO-BT and NO-CS) and SO were developed and investigated using the finite volume method. Conduits of 3, 3.5 and 4 mm were used in the NO models, whereas conduits of 4, 5 and 6 mm were used in the SO model. The hydraulic nets (lumped resistances, compliances, inertances and elastances) which represent the systemic, coronary and pulmonary circulations and the heart were identical in the two models. A multiscale approach was adopted to couple the 3-D models with the circulation net. Computer simulation results were compared with post-operative catheterization data. Results showed that (i) there is a good correlation between predicted and observed data: higher aortic diastolic pressure, decreased pulmonary arterial pressure, lower pulmonary-to-systemic flow ratio and higher coronary perfusion pressure in SO; (ii) there is a minimal regurgitant flow in the SO conduit. The close correlation between predicted and observed clinical data supports the use of mathematical modelling, with a mandatory multiscale approach, in the design and assessment of surgical procedures.

Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular fibrillation cardiac arrest in pigs

Since adrenaline (epinephrine) also has negative effects during and after cardiopulmonary resuscitation (CPR) a non-adrenergic vasoconstrictor like endothelin might be an alternative to increase vital organ blood flow. We studied the effect of different doses of endothelin-1 compared with adrenaline on the ability to resuscitate, cerebral and myocardial blood flow (MBF) in a closed chest cardiac arrest pig model. After 5 min of ventricular fibrillation, CPR with a ventilator and a mechanical compression device was started. At 10 min, 31 pigs were randomized to receive a single dose of endothelin-1 50, 100 or 200 μg or repeated doses of adrenaline 0.04 mg kg −1 or saline every 3 min. After 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation. Blood flow was measured with the fluorescent microsphere method. In animals receiving endothelin-1 50, 100 and 200 μg the cerebral blood flow (CBF) increased from median 28 (25th; 75th quartile: 16; 40), 32 (15; 48) and 17 (4; 65) to 36 (31; 54), 47 (39; 57) and 63 (35; 83) ml min −1 per 100 g, respectively, 6 min after drug administration ( P<0.05 endothelin-1 50 μg vs. Control, P<0.01 endothelin-1 100 and 200 μg vs. Control). At the same time CBF decreased in the control and adrenaline group from 36 (21; 41) and 39 (15; 50) to 12 (2; 25) and 24 (15; 26) ml min −1 per 100 g, respectively, ( P<0.05 adrenaline vs. endothelin-1 200 μg). There was no difference in MBF between the treatment groups despite a higher coronary perfusion pressure (CoPP) in the endothelin-1 groups. Restoration of spontaneous circulation could be only achieved in the endothelin-1 50 μg (3 of 7; 43%) and 100 μg (5 of 7; 71%) group. This study suggests that endothelin-1 enhances CBF during CPR better than adrenaline and increases resuscitation success.

Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis

To evaluate the effects of resuscitation with a 10% diaspirin-crosslinked hemoglobin (DCLHb) solution on global hemodynamic variables, systemic and myocardial oxygen transport and tissue oxygenation, and contractile function of the left ventricle in an experimental model of severe hemorrhagic shock and critical stenosis of the left anterior descending coronary artery (LAD). Prospective, placebo-controlled, randomized study. Experimental animal laboratory. A total of 20 anesthetized pigs. After implementation of a permanent critical LAD stenosis (ie, maintenance of basal blood flow but absence of reactive hyperemia after a 10-sec complete vessel occlusion), hemorrhagic shock (target mean aortic pressure, 45 mm Hg) was induced within 15 mins by programmed withdrawal of blood and maintained for 60 mins. Subsequently, the volume of plasma lost during hemorrhage was replaced by either a balanced electrolyte solution containing 10 g/dL DCLHb (DCLHb group; n = 10) or an 8 g/dL human albumin solution (HSA) oncotically matched to DCLHb (HSA group; n = 10). Data were collected immediately after the infusion of the different solutions and again after 60 mins had elapsed. Although five of ten HSA-treated animals died of acute left ventricular failure within the first 20 mins after complete fluid resuscitation, all of the DCLHb-treated animals survived the 60-min observation period after resuscitation (p < .05). This significant difference in mortality is explained by higher coronary perfusion pressure in DCLHb-treated animals (75 +/- 17 vs. 27 +/- 17 torr DCLHb vs. HSA group; p < .05) and persistence of subendocardial ischemia and hypoxia (radioactive microspheres method) in HSA-treated animals on resuscitation particularly affecting the LAD-supported myocardium (subendocardial oxygen delivery: 20 +/- 11 vs. 3 +/- 1 mL oxygen x g(-1) x min(-1), DCLHb vs. HSA group; p < .05). Except for enhanced myocardial contractility immediately on infusion of DCLHb (maximal left ventricular pressure increase: 2373 +/- 782 vs. 1730 +/- 543 torr x sec(-1) DCLHb vs. HSA group; p < .05), no differences were detected between groups concerning the variables of systemic oxygen transport, tissue oxygenation, and regional contractile function of the myocardium (determined with microsonometry). Fluid resuscitation with 10% DCLHb solution completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia in the presence of compromised coronary circulation and thereby prevents early death after resuscitation.

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs.

To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.

Complete Unloading Alone May Not Adequately Protect the Left Ventricle

The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.

Selective Aortic Arch Perfusion During Cardiac Arrest: Enhanced Resuscitation Using Oxygenated Perflubron Emulsion, With and Without Aortic Arch Epinephrine

Study objective: To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. Methods: This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. Results: Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1±1.9 minutes in the AoE-SAAP group, compared with 11.0±5.8 minutes in the IVE-SAAP group. Conclusion: SAAP with oxygenated perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC. [Manning JE, Batson DN, Payne FB, Adam N, Murphy CA, Perretta SG, Norfleet EA: Selective aortic arch perfusion during cardiac arrest: Enhanced resuscitation using oxygenated perflubron emulsion, with and without aortic arch perfusion. Ann Emerg Med May 1997; 29:580-587.]

Reperfusion at reduced flow rates enhances postischemic contractile recovery of perfused heart

The effects of reperfusion at reduced flow rates on postischemic cardiac contractile function were examined in perfused rat hearts. Isolated hearts were subjected to 35-min ischemia followed by reperfusion at the preischemic flow rate (9.0 ml.g-1.min-1; ordinary flow rate) or at reduced flow rates (0.9-8.1 ml.g-1.min-1). Reperfusion at ordinary flow rate did not generate any left ventricular developed pressure (LVDP), whereas reperfusion at reduced flow rates (0.9-7.2 ml.g-1.min-1) elicited 13-57% of initial contractile force at reperfusion's end; optimal recovery occurred at 3.6 ml.g-1.min-1 (reduced flow rate). Reduced flow rate reperfusion attenuated ischemia-reperfusion-induced increase in left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP), alteration in tissue Na+, K+, Ca2+, and Mg2+, release of creatine kinase and ATP metabolites, and development of triphenyltetrazolium chloride-unstained areas. Enhanced postischemic LVDP recovery was inversely related to higher coronary PP at the initial stage (4 min) of reperfusion (r = -0.763). The benefit of reduced flow rate reperfusion could not be attributed to rate of calcium delivery to the heart, formation of oxygen free radicals in myocardium, endothelium-dependent coronary artery dilation, or LVDEP reduction. Enhancement of postischemic LVDP recovery was associated with attenuation of ischemia-reperfusion-induced increases in myocardial sodium and calcium; failure of postischemic LVDP recovery was accompanied by an increase. Reduction in sodium and calcium overload may underlie the beneficial effects of reduced flow rate reperfusion in ischemic-reperfused heart.

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

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. Prospective, block randomized, blinded, placebo-controlled, laboratory study. Thirty mixed breed canines. 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. 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. 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.