Paul Lindstrom

Improving Standard Cardiopulmonary Resuscitation with an Inspiratory Impedance Threshold Valve in a Porcine Model of Cardiac Arrest

To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we evaluated the potential value of impeding respiratory gas exchange selectively during the decompression phase of standard CPR in a porcine model of ventricular fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs weighing 30 kg were randomized to be treated with either standard CPR with a sham valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold valve (ITV™) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic minus right atrial pressure) was the primary endpoint. Vital organ blood flow was assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation was attempted 11 min after starting CPR. After 2 min of CPR, mean ± sem CPP was 14 ± 2 mm Hg with the sham valve versus 20 ± 2 mm Hg in the ITV group (P < 0.006). Significantly higher CPPs were maintained throughout the study when the ITV was used. After 6 min of CPR, mean ± sem left ventricular and global cerebral blood flows were 0.10 ± 0.03 and 0.19 ± 0.03 mL · min−1 · g−1 in the Control group versus 0.19 ± 0.03 and 0.26 ± 0.03 mL · min−1 · g−1 in the ITV group, respectively (P < 0.05). Fifteen minutes after successful defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in the ITV group (not significant). In conclusion, use of an inspiratory impedance valve during standard CPR resulted in a marked increase in CPP and vital organ blood flow after 6 min of cardiac arrest.

Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest.

ObjectiveThis study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest. DesignProspective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation. SettingUniversity hospital laboratory. SubjectsEighteen piglets weighing 8–11 kg. InterventionsAsphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 &mgr;g/kg epinephrine (n = 6), or a combination of 45 &mgr;g/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration. Measurements and Main ResultsMean ± sem coronary perfusion pressure, before and 2 mins after drug administration, was 13 ± 2 and 23 ± 6 mm Hg in the vasopressin group; 14 ± 2 and 31 ± 4 mm Hg in the epinephrine group; and 13 ± 1 and 33 ± 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean ± sem left ventricular myocardial blood flow was 44 ± 31 and 44 ± 25 mL·min−1·100 g−1 in the vasopressin group; 30 ± 18 and 233 ± 61 mL·min−1·100 g−1 in the epinephrine group; and 36 ± 10 and 142 ± 57 mL·min−1·100 g−1 in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin;p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 ± 19 mL·min−1·100 g−1) than after vasopressin (36 ± 17 mL·min−1·100 g−1) or epinephrine alone (31 ± 7 mL·min−1·100 g−1;p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine). ConclusionsAdministration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation.

ObjectiveWe recently demonstrated that vasopressin alone resulted in a poorer outcome in a pediatric porcine model of asphyxial cardiac arrest when compared with epinephrine alone or with epinephrine plus vasopressin in combination. Accordingly, this study was designed to differentiate whether the inferior effects of vasopressin in pediatrics were caused by the type of cardiac arrest. DesignProspective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SettingUniversity hospital laboratory. SubjectsEighteen piglets weighing 8–11 kg. InterventionsAfter 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 &mgr;g/kg epinephrine (n = 6), or a combination of 45 &mgr;g/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200 &mgr;g/kg epinephrine, or a combination of 200 &mgr;g/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation. Measurements and Main ResultsMean ± sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 ± 4 and 70 ± 13 mL·min−1·100 g−1 in the vasopressin group; 83 ± 42 and 85 ± 41 mL·min−1·100 g−1 in the epinephrine group; and 176 ± 32 and 187 ± 29 mL·min−1·100 g−1 in the epinephrine-vasopressin group (p < .006 after both doses of epinephrine-vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin vs. epinephrine, respectively). At the same times, mean ± sem total cerebral blood flow was 73 ± 3 and 47 ± 5 mL·min−1·100 g−1 after vasopressin; 18 ± 2 and 12 ± 2 mL·min−1·100 g−1 after epinephrine; and 79 ± 21 and 41 ± 8 mL·min−1·100 g−1 after epinephrine-vasopressin (p < .025 after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine). Five of six vasopressin-treated, two of six epinephrine-treated, and six of six epinephrine-vasopressin treated animals had return of spontaneous circulation (nonsignificant). ConclusionsIn this pediatric porcine model of ventricular fibrillation, the combination of epinephrine with vasopressin during cardiopulmonary resuscitation resulted in significantly higher levels of left ventricular myocardial blood flow than either vasopressin alone or epinephrine alone. Both vasopressin alone and the combination of epinephrine with vasopressin, but not epinephrine alone, improved total cerebral blood flow during cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest, vasopressin alone or in combination with epinephrine appears to be of benefit after ventricular fibrillation in the pediatric porcine model.

Synergistic effects of vasopressin plus epinephrine during cardiopulmonary resuscitation

Both epinephrine (Epi) and vasopressin (VP) increase coronary perfusion pressure (CPP) when administered during cardiac arrest. Given their different mechanisms of action we tested the hypothesis that during cardiopulmonary resuscitation (CPR) a combination of VP plus Epi would be superior to either agent alone. Epi(40 microg/kg), VP(0.3 U/kg) and the combination of both agents were assessed in a porcine model of ventricular fibrillation (VF). Maximum CPP (diastolic aortic-right atrial pressures) during CPR was similar among the groups but the time course of action was different in each group: with Epi + VP the increase in CPP was significantly more rapid than with VP alone whereas the CPP remained significantly higher for a longer periods of time with VP or VP + Epi versus Epi alone. Left ventricular blood flow (ml/min per g) determined during CPR two min after drug administration was similar between groups: Epi 1.06 +/- 0.16; VP 0.82 +/- 0.26; Epi + VP 0.83 +/- 0.14 (P = N.S.). Post drug administration. 2 min, cerebral blood flow (ml/min per g) in the VP group (0.76 +/- 0.15) was more than two times higher compared with Epi alone (Epi:0.30 +/- 0.08, P < 0.01 versus VP) and Epi plus VP (Epi + VP:0.23 +/- 0.03, P < 0.01 versus VP). We conclude that combination of VP + Epi during cardiac arrest results in a more rapid rise in CPP when compared with VP alone and a more sustained elevation in CPP than observed with Epi alone. Thus, the synergistic effects of these two potent vasopressor agents may be of benefit during CPR.

Coronary Nitric Oxide Production in Response to Exercise and Endothelium-Dependent Agonists

BACKGROUND Endothelium-derived nitric oxide (NO) contributes to epicardial coronary artery vasodilation during exercise. However, blockade of NO production does not impair the increase in coronary blood flow (CBF) during exercise, suggesting that NO is not obligatory for exercise-induced coronary resistance vessel dilation. In contrast, the increases in CBF produced by endothelium-dependent agonists are decreased after NO blockade. Consequently, this study was performed to determine whether the increase in coronary NO production in response to agonists is greater than that which occurs during exercise. METHODS AND RESULTS We measured the oxidation products of NO (nitrate+nitrite=NO(x)) in aortic and coronary sinus plasma using chemiluminescence to assess NO(x) production across the coronary circulation in chronically instrumented dogs during a 3-stage treadmill exercise protocol and in response to intracoronary administration of the endothelium-dependent agonists acetylcholine (37.5 microg/min) and bradykinin (3.0 microg/min). No coronary NO(x) production could be detected at rest or during the first 2 stages of exercise; only at the highest level of exercise was a small increase in coronary NO(x) production measured. In contrast, coronary production of NO(x) was significantly increased in response to endothelium-dependent agonists. CONCLUSIONS Coronary NO production in response to endothelium-dependent agonists is greater than in response to the increase in shear stress associated with exercise. These findings support previous studies suggesting that NO is not required for the coronary vasodilation that occurs in the normal heart during exercise.

Comparison of epinephrine with vasopressin on bone marrow blood flow in an animal model of hypovolemic shock and subsequent cardiac arrest

ObjectiveThe intraosseous route is an emergency alternative for the administration of drugs and fluids if vascular access cannot be established. However, in hemorrhagic shock or after vasopressors are given during resuscitation, bone marrow blood flow may be decreased, thus impairing absorption of intraosseously administered drugs. In this study, we evaluated the effects of vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on bone marrow blood flow. DesignProspective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SettingUniversity hospital laboratory. SubjectsFourteen pigs weighing 30 ± 3 kg. InterventionsRadiolabeled microspheres were injected to measure bone marrow blood flow during a prearrest control period and during hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood volume. In the second part of the study, ventricular fibrillation was induced; after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary resuscitation, a bolus dose of either 200 &mgr;g/kg epinephrine (n = 6) or 0.8 units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5 mins after drug administration, and blood flow was assessed again at 5 and 30 mins after successful resuscitation. Measurements and Main Results Mean ± sem bone marrow blood flow decreased significantly during induction of hemorrhagic shock from 14.4 ± 4.1 to 3.7 ± 1.8 mL·100 g−1·min−1 in the vasopressin group and from 18.2 ± 4.0 to 5.2 ± 1.0 mL·100 g−1·min−1 in the epinephrine group (p = .025 in both groups). Five minutes after return of spontaneous circulation, mean ± sem bone marrow blood flow was 3.4 ± 1.1 mL·100 g−1·min−1 after vasopressin and 0.1 ± 0.03 mL·100 g−1·min−1 after epinephrine (p = .004 for vasopressin vs. epinephrine). At the same time, bone vascular resistance was significantly (p = .004) higher in the epinephrine group when compared with vasopressin (1455 ± 392 vs. 43 ± 19 mm Hg· mL−1·100 g·min, respectively). ConclusionsBone blood flow responds actively to both the physiologic stress response of hemorrhagic shock and vasopressors given during resuscitation after hypovolemic cardiac arrest. In this regard, bone marrow blood flow after successful resus-citation was nearly absent after high-dose epinephrine but was maintained after high-dose vasopressin. These findings emphasize the need for pressurized intraosseous infusion techniques, because bone marrow blood flow may not be predictable during hemorrhagic shock and drug therapy.

Subendocardial and subepicardial wall thickening during ischemia in exercising dogs

To determine whether ischemia in the exercising dog is associated with preservation of subepicardial thickening relative to subendocardial thickening, 10 dogs were chronically instrumented with circumflex artery flow probes, hydraulic occluders, and pairs of ultrasonic microcrystals for determination of wall thickness in the circumflex artery distribution. One pair of crystals spanned the entire ventricular wall (transmural), and the other spanned the outer half of the ventricular wall. Inner wall thickness was computed as the difference between transmural wall thickness and outer wall thickness. Dogs performed control treadmill exercise and exercise with a coronary stenosis that reduced circumflex artery flow to resting control levels. Percent systolic thickening at rest for the transmural, inner, and outer regions was 21.3 +/- 11.8%, 35.5 +/- 20.3%, and 10.3 +/- 5.0% (mean +/- SD), respectively. During exercise without stenosis, systolic thickening increased to 143 +/- 37% of control for outer wall crystals and 137 +/- 26% of control for the inner portion of the wall. During exercise, the addition of a coronary stenosis caused a reduction in thickening to 17.7 +/- 28.5% of control for the outer wall and 40.1 +/- 32.3% of control for the inner portion of the wall; these were not significantly different. In contrast, normalized inner wall blood flow during exercise with circumflex artery stenosis (25.0 +/- 16.0%) was significantly less than for the outer portion of the wall (48.5 +/- 20.9%). Further, there was a close relation between changes in inner wall thickening and inner wall blood flow (r = 0.84), whereas there was only a very weak relation between changes in outer wall blood flow and function (r = 0.62; p = 0.04). During ischemia in the exercising dog, outer wall thickening is depressed out of proportion to reductions in outer wall blood flow and is not preserved relative to inner wall thickening.