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(TM)) (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.

Spatially localized phosphorus-3 I nuclear magnetic resonance ( 3'P NMR) spectroscopy has been applied to the study of the normal canine myocardium to measure the relative content of high energy phosphates across the left ventricular wall. Transmural NMR data were acquired in five voxels spanning the wall of the left ventricle using the FLAX-ISIS technique. The validity of the FLAX-ISIS approach in acquiring localized spectra for transmural studies and in providing quantitative information from the localized spectra was examined rigorously by studies involving phantoms, intact rats, and the canine myocardium in vivo. The results indicated that ( 1 ) this technique yields spatially resolved spectra with partial overlap between adjacent voxels and virtually no overlap between every other voxel; ( 2 ) in the canine heart, signals from subepicardium, midwall, and subendocardium can be detected separately without cross contamination; and (3 ) relative metabolite contents within a voxel and among voxels can be quantitated. Transmural 3'P NMR spectra were acquired with cardiac gating on 29 separate animals either at early systole or late diastole, and at three different workloads with the heart rate peak systolic pressure product (RPP) increasing from 6000 mmHg/min to 35,000 mmHg/min. The data revealed that in the normal canine myocardium, the creatine phosphate (CP) content and the CP/ATP ratio was significantly lower in the subendocardium than in the subepicardium. ATP levels were transmurally constant. Both the CP content and the CP/ATP ratio measured for each voxel remained unaltered in relation to either the phase of the cardiac cycle or -fourfold increase in workload. Free ADP levels calculated for each voxel showed that ADP was relatively higher in the subendocardium than the subepicardium, and in all transmural layers was higher than its apparent K,,, for oxidative phosphorylation. In this domain changes in ADP content with workload and MV02 are not expected and were not observed.

Phosphorus-31 nuclear magnetic resonance (31P NMR) has been applied to study the canine heart prior to and during regional myocardial ischemia induced by partial flow reduction in the left anterior descending coronary artery (LAD). NMR data were acquired in a transmural fashion by restricting the signal to a column perpendicular to the heart wall using B0 gradients and obtaining spectroscopic spatial resolution along the third dimension using the B1 gradient and adiabatic excitation. With this approach, transmural spectra were accumulated in five separate voxels spanning the wall of the left ventricle from the epicardium to the endocardium. In the normal canine myocardium the levels of high-energy phosphates CP and ATP were relatively constant throughout the left ventricular wall, with only minor evidence of free inorganic phosphate in any of the transmural voxels. However, during sustained partial occlusion of the LAD, significant regional differences between the epi- and the endocardium were noted. The data demonstrate the importance of studying cardiac bioenergetics with transmural differentiation.

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 μg/min) and bradykinin (3.0 μg/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.

Administration 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.

To determine whether progressive regional myocardial dysfunction occurs after repetitive episodes of exercise-induced ischemia, 10 dogs were instrumented with ultrasonic microcrystals for determination of regional myocardial wall thickening, circumflex artery electromagnetic flow probes, and hydraulic coronary artery occluders. Dogs performed treadmill exercise in the presence of a coronary artery stenosis, which limited coronary blood flow to control levels. Dogs performed a single 10-min exercise period one day and three identical runs separated by 1-h rest periods on the alternate day. At rest before the first exercise period, circumflex wall thickening was 18.8 +/- 6.7% and increased to 25.5 +/- 10.6% during exercise before the application of coronary stenosis. On the day that three exercise trials were performed, circumflex systolic wall thickening at rest before the third exercise period (9.7 +/- 4.0%) and during exercise without coronary stenosis (17.3 +/- 7.3%) were both significantly lower than during the first exercise period (P less than 0.0125). During exercise with stenosis, circumflex systolic wall thickening fell to 4.6 +/- 4.7% during a single run, and 5.0 +/- 2.0% during the third of three consecutive runs. Wall thickening was significantly lower 2 h after the third consecutive run (9.1 +/- 2.4%) than 2 h after a single period of exercise-induced ischemia (14.8 +/- 7.6%; P 0.0125). Transmural myocardial blood flow to circumflex myocardium during the third period of exercise-induced ischemia (0.93 +/- 0.47 ml.min-1.g-1) was not different than during the single period of exercise (0.84 +/- 0.47 ml.min-1.g-1). It is concluded that repetitive episodes of exercise-induced ischemia result in cumulative postexercise regional myocardial dysfunction.

This study was carried out to determine the relative importance of alpha 1- and alpha 2-adrenergic vasoconstriction in opposing the increase in coronary blood flow, which occurs during exercise. The response of left circumflex coronary artery blood flow was examined during treadmill exercise in 16 chronically instrumented dogs during control conditions, after selective alpha 1-adrenergic blockade with intracoronary prazosin, and after alpha 2-blockade with intracoronary idazoxan. During control conditions, graded treadmill exercise resulted in progressive increases of coronary blood flow and decreases of coronary vascular resistance. Prazosin produced highly selective alpha 1-adrenergic blockade; coronary blood flow was significantly higher and coronary vascular resistance significantly lower during all but the heaviest exercise stage after prazosin. Idazoxan produced highly effective, but only moderately selective, alpha 2-adrenergic blockade. However, after idazoxan, coronary blood flow and coronary vascular resistance during exercise were not significantly different from control. Combined alpha 1- and alpha 2-adrenergic blockade was not more effective in increasing coronary blood flow during exercise than was alpha 1-adrenergic blockade alone. These data support a role for alpha 1-adrenergic coronary vasoconstriction in limiting the increase in coronary blood flow, which occurs during exercise, but do not support a role for alpha 2-mediated coronary vasoconstriction during exercise.

In 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.