The relationship of carbon dioxide excretion during cardiopulmonary resuscitation to regional blood flow and survival.

Currently, there are no practical means of prospectively determining cardiopulmonary resuscitation (CPR) adequacy in the field. Airway CO2 excretion can be noninvasively and stably measured under changing environmental conditions. We investigated the relationships between the volume of airway CO2 excreted (CO2EX) during CPR to regional blood flow (RBF) and survival. A total of 21 dogs were randomly divided into four CO2EX groups (< 5, 5-6, > 6-7 and > 7 ml CO2/min per kg), anesthetized, instrumented and ventilated with an in-line infrared airway CO2 sensor. Anesthesia was reduced and baseline measurements made. Ventricular fibrillation (VF) was initiated and resuscitation withheld for 3 min, followed by 17 min of CPR. Compression force alone was adjusted to maintain predetermined CO2EX. Animals were resuscitated, monitored for 2 h and observed for an additional 22 h. RBF was determined at baseline, 16 min post-VF and 60 min post-resuscitation. Mean CO2EX during CPR was significantly higher in survivors than nonsurvivors. The probability of survival increased as CO2EX increased. The highest CO2EX group had the highest rate of survival (86%), but did not always have significantly higher cardiac output (CO), myocardial or cerebral blood flows (MBF, CBF) than the lowest CO2EX group with a 0% survival rate. These data suggest survival is tracked better by CO2EX than by CO, MBF or CBF. Therefore, CO2EX appears to provide a practical reliable noninvasive method of determining CPR efficacy in the field.

The relationship between airway carbon dioxide excretion and cardiac output during cardiopulmonary resuscitation.

There is currently no practical method for determining cardiopulmonary resuscitation (CPR) efficacy in the field. We investigated the relationship between the volume of carbon dioxide (CO2) excreted in the airway (CO2EX) when tidal volume and respiratory rate are controlled, and cardiac output (CO), an indicator of CPR efficacy, to determine the potential of CO2EX as a practical noninvasive field monitor of CPR efficacy. Thirteen mongrel dogs were anesthetized, instrumented and ventilated 13 times/min at a fixed tidal volume with an infrared airway CO2 sensor. CO2EX = (PCO2/bar. press) x (tidal vol) x (breaths/min), and expressed in ml/min per kg. Sequences of control, CPR with 3-4 different compression forces, and recovery measurements were recorded 10-15 times/animal. CO2EX and CO fell simultaneously with ventricular fibrillation. CPR immediately increased CO2EX and CO. Both changed consistently and in the same direction as compression force. Return of spontaneous circulation immediately increased CO2EX and CO above controls, with a gradual return to control levels. CO2EX was always below 8 ml-CO2/min/kg during CPR and above this during spontaneous circulation. With alveolar ventilation controlled, CO2 movement is regulated by CO, CO distribution and CO2 stores shifts. Normally, CO accounts for 15% of CO2EX variability. In this study CO accounted for > or = 65% of CO2EX variability during CPR, indicating CO2EX changes were primarily due to CO changes. When ventilation is controlled, CO2EX during CPR reliably tracks changes in CO. Therefore, CO2EX may provide a practical noninvasive method of determining CPR efficacy as the CPR is being performed.

Stratification of the risk of thrombosis after intracoronary stenting for threatened or acute closure complicating coronary balloon angioplasty: a Cook registry study.

This study was carried out to stratify the risk of stent thrombosis by using three predictors: stent size, poststenting residual dissection, and residual filling defect. In the multicenter clinical trial, 1318 patients had successful deployment of Gianturco-Roubin coronary stent for threatened and acute closure. The 714 (54.2%) patients having none of these risk factors were designated a low-risk group; 484 (36.6%) had one factor and were designated an intermediate-risk group; 120 (9.1%) had two or all three factors and were designated a high-risk group. The incidence of stent thrombosis was 5.6%, 9.4%, and 16.7% in the low-, intermediate-, and high-risk groups; the difference among the three groups was highly significant (p < 0.0001). With these three predictors, the risk of stent thrombosis can be stratified. Avoiding the use of small stents (< 3.0 mm) and achieving optimal angiographic results after stenting for acute or threatened closure are useful strategies in reducing stent thrombosis.

An acoustical guidance and position monitoring system for endotracheal tubes.

A prototype instrument to guide the placement and continuously monitor the position of an endotracheal tube (ETT) was developed. An incident audible sound pulse is introduced into the proximal ETT and detected as it travels down the ETT via a miniature microphone located in the wall. This pulse is then emitted from the tube tip into the airways and the reflected signal from the airways is detected by the microphone. A well defined reflection arises from the point where the total cross sectional area of the airways increases rapidly, and the difference in timing between detection of the incident pulse and this reflection is used to determine ETT position or movement. This reflection is not observed if the ETT is erroneously placed in the esophagus. The amplitude and polarity of an additional reflection that occurs at the ETT tip is used to estimate the cross-sectional area of the airway in which the ETT is placed. This combined information allows discrimination between tracheal and bronchial intubation and can be used to insure an adequate fit between the ETT and trachea. The instrument has proven extremely reliable in multiple intubations in eight canines and offers the potential to noninvasively and inexpensively monitor ETT position in a continuous manner.

Detection of ventricular tachycardia and fibrillation using coronary sinus blood temperature: a feasibility study.

This study investigated the potential of coronary sinus blood temperature to detect ventricular arrhythmias. A rapid-response, thermistor-tipped catheter placed in the coronary venous system of anesthetized dogs was used to record the blood temperature during periods of induced bradycardia, tachycardia, and ventricular fibrillation. A second catheter was used to measure blood temperature in the aortic arch during these same episodes. A pulsatile component of venous blood temperature, typically 40 m degrees C in amplitude, was well correlated with the cardiac cycle, while another, slightly larger, pulsatile component was well correlated with respiration. The cardiac component peaked during ventricular systole, and the respiratory component peaked during expiration. As compared with sinus rhythm, the cardiac signal diminished during bradycardia and tachycardia and nearly disappeared during asystole and ventricular fibrillation. The baseline component of venous blood temperature rose during periods of tachycardia and fibrillation, while respiration proved to be an important factor in the baseline temperatures. The presence of small, cyclic, thermal variations in the coronary venous system was verified, and the concept of measuring metabolic activity to assess ventricular function was substantiated. These studies show promise that this concept could be incorporated into medical devices that use these temperature signals for diagnosis of ventricular arrhythmias.

Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes.

OBJECTIVES: This study reports on the initial experience with the Gianturco-Roubin flexible coronary stent. The immediate and 6-month efficacy of the device and the incidence of the complications of death, myocardial infarction, emergency coronary artery bypass surgery and recurrent ischemic events are presented. BACKGROUND: Abrupt or threatened vessel closure after coronary angioplasty is associated with increased risk of myocardial infarction, emergency coronary artery bypass graft surgery and in-hospital death. When dissection or prolapse of dilated plaque into the lumen is unresponsive to additional or prolonged balloon catheter inflation, coronary stenting offers a nonsurgical mechanical means to rapidly restore stable vessel geometry and adequate coronary blood flow. METHODS: From September 1988 through June 1991, 518 patients underwent attempted coronary stenting with the 20-mm long Gianturco-Roubin coronary stent for acute or threatened vessel closure after angioplasty. In 494 patients, one or more stents were deployed. Thirty-two percent of patients received stents for acute closure and 69% for threatened closure. RESULTS: Successful deployment was achieved in 95.4% of patients. Overall, stenting resulted in an immediate angiographic improvement in the diameter stenosis from 63 +/- 25% before stenting to 15 +/- 14% after stenting. Emergency coronary artery bypass graft surgery was required in 4.3% (21 of 493 patients). The incidence of in-hospital myocardial infarction (Q wave and non-Q wave) was 5.5% (27 of 493 patients). At 6 months, myocardial infarction was infrequent, occurring in 1.6% (8 of 493 patients). The incidence of in-hospital death was 2.2% (11 of 493 patients). Late death occurred in 7 patients (1.4%) and 34 patients (6.9%) required later bypass graft surgery. Complications included blood loss, primarily from the arterial access site, and subacute thrombosis of the stented vessel in 43 patients (8.7%). CONCLUSIONS: The early multicenter experience suggests that this stent is a useful adjunct to coronary angioplasty to prevent or minimize complications associated with flow-limiting coronary artery dissections previously correctable only by surgery. Although this study was not randomized, it demonstrated a high technical success rate and encouraging results with respect to the low incidence of emergency coronary artery bypass graft surgery and myocardial infarction.

Continuous monitoring of cerebral perfusion by thermal clearance.

Currently, no commercially available system exists to continuously monitor the effective tissue perfusion within the parenchyma of the brain. While several methods exist for accurately measuring cerebral perfusion; among them: 133xeonon clearance, hydrogen clearance and radiolabeled microsphere injection; none of these methods provides continuous monitoring. The Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System (Bloomington, IN, USA) was initially developed to treat brain tumours by maintaining constant, moderate hyperthermia within a defined tissue volume over an extended duration. The system continuously adjusts the power applied to heating elements in order to maintain a constant temperature within the treatment volume. Because tissue perfusion is a primary factor responsible for removing heat from tissue, monitoring the amount of power applied to the heating elements allows one to continuously estimate tissue perfusion in the vicinity of the heating elements. In the current study, regional blood flow in the vicinity of heater/sensor catheters implanted in the brain parenchyma of three dogs was estimated by the VH8500 tissue perfusion algorithm and directly measured with radioactive labeled microspheres. The accuracy of the perfusion estimate (Thermal Perfusion Index) was evaluated by comparing these values. A range of blood flow was achieved in each animal by infusing nitroprusside. It was found that with the perfusion estimation algorithm of the Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System as it is currently implemented, the Thermal Perfusion Index tended to underestimate regional perfusion as measured with radioactive microspheres, but the relationship was nearly linear. Thus, the system currently tracks changes in regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of motor-evoked potential response to ischemic spinal cord damage.

The prevalence of morbidity is a major deterrent to the success of aortic aneurysm replacement operations. We have developed a model of spinal cord ischemia, based on the amplitude reduction of the motor-evoked potential, which produces approximately a 90% prevalence of paraplegia. Regional blood flow was studied with the use of radioactive microspheres, and results showed that there was a significant decrease in flow to the lumbar cord (85% reduction) during aortic occlusion, followed by a twofold to threefold hyperemia that persisted for 24 hours. Histopathologic examination of the cord revealed that the greater portion of microgliosis, spongiosis, and neuronal damage was confined to the gray matter of the cord, and its severity increased as one progressed caudally. The somatosensory-evoked potential disappeared before the motor-evoked potential L-2 signal in all dogs, with a mean disappearance time of 10.9 +/- 5.6 minutes, compared with 21 +/- 6.6 minutes for the motor-evoked potential. Both the sensory-evoked potential and the motor-evoked potential cord signal were present 24 hours later in all dogs tested. The peripheral nerve motor-evoked potential disappeared within 1 minute of cord ischemia, was not present 24 hours later, and hence appears to be too sensitive to use as an indicator of spinal cord damage. Plotting spinal cord motor-evoked potential amplitude reduction versus both histopathologic damage and regional blood flow revealed a positive correlation between motor-evoked potential amplitude reduction, decreased cord perfusion, and increased histopathologic damage. In addition, it may be possible to make inferences about the neurologic status of a subject based on the magnitude and time-course of the motor-evoked potential's amplitude reduction and wave morphology.

The chronaxie for myocardium and motor nerve in the dog with chest-surface electrodes.

The chronaxie (i.e., the duration for a stimulating current having twice the rheobasic, or minimum, value) was determined for ventricular myocardium in 12 pentobarbital-anesthetized dogs. Current was applied transthoracically via chest-surface electrodes located at the optimal axillary site for producing inspiration by stimulation of the phrenic nerve (electroventilation). In four dogs the chronaxie for motor-nerve was determined using electrodes at the same location. After using hand-held electrodes to identify the optimal stimulation site for electroventilation, 4.1 cm diameter electrodes were applied bilaterally to the optimal site on the thorax. In 12 dogs, the threshold current for producing ventricular ectopic beats was determined for single rectangular current pulses ranging from 0.1-10 ms in duration. From these data, strength-duration curves were determined and the average chronaxie for ventricular myocardium was found to be 1.82 ms. In four dogs the relationship between inspired volume and maximum stimulus intensity was determined using a 0.8 s burst of stimuli (60/s) with pulse durations ranging from 20-500 microseconds. From these data, strength-duration curves for current were constructed and the average chronaxie for motor-nerve was found to be 0.17 ms. The results of this study show that, because of the differing chronaxies, the current required to produce inspiration with short-duration stimuli is much less than that required to evoke an ectopic heart beat.

Ventricular fibrillation produced by stimulation of external transthoracic electrodes--an experimental study.

The threshold for ventricular fibrillation was determined in 12 pentobarbital anesthetized dogs using transthoracic electrodes located at the optimal axillary electroventilation sites. Electroventilation is the name used to designate inspiration produced by stimuli applied to body surface electrodes. The optimal stimulation site for electroventilation was first determined using hand-held electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal anterior axillary stimulation site. The threshold current for producing ventricular fibrillation was determined using single pulses ranging from 0.1-10 msec in duration delivered during the vulnerable period of the cardiac cycle. Fibrillation was produced in all dogs with the 10- and 5-msec pulse durations, in 11 dogs with 0.3-msec, in 6 dogs with 0.2-msec, and in 1 dog with 0.1-msec pulse duration. In all dogs, the current required to produce ventricular fibrillation increased greatly as the pulse duration was decreased. The current required for fibrillation was much in excess of that required to produce one tidal volume. With the longer duration pulses, the ratio was about 80. With the 8 microseconds duration pulses used for electroventilation the estimated ratio is about 800.

Artificial respiration in the anesthetized horse using bilateral, percutaneous, cervical phrenic-nerve stimulation with needle electrodes: a preliminary report.

In this preliminary study, artificial respiration was produced in four anesthetized horses using trains of stimuli applied to long needle electrodes inserted bilaterally at the base of the neck. The needles were insulated to within 1 cm of the tips. The frequency of the stimuli (0.1 msec) was 35/sec and the train duration (duration of inspiration) was 1 sec. Inspired volume increased with increasing stimulus intensity. In two animals, inspired volumes of 6 liters were achieved. In another animal 4.5 liters was achieved and in another, 2.5 liters. This lower value probably represented less-than-optimal electrode placement. Artificial percutaneous electrophrenic respiration was maintained for half an hour in every animal using a minute volume equivalent to that when breathing spontaneously.

Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury.

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase. Previous work has indicated that methylene blue accepts electrons from xanthine oxidase at the iron-sulfur center. Initial experiments in our laboratory demonstrated that (1) pairs of electrons from each enzymatic oxidation are transferred to methylene blue, (2) the reduction of methylene blue can be achieved by model iron-sulfur centers, similar to the iron-sulfur center of xanthine oxidase, (3) reduced methylene blue auto-oxidizes to produce H2O2 directly, rather than O2-, and (4) methylene blue is effective at non-toxic levels (2-5 mg/kg) in preventing free radical damage to liver and kidney tissues in an in vitro model of ischemia and reoxygenation. Accordingly, we propose that methylene blue may represent a new class of antioxidant drugs that competitively inhibit reduction of molecular oxygen to superoxide by acting as alternative electron acceptors for tissue oxidases. We have termed these agents "parasitic" electron acceptors.

The effects of soman poisoning in combination with hypovolemic shock.

Hemorrhage is a cause of death in both combat and civilian injuries. The specific objectives of this research were: (1) to determine the pathophysiologic effects of combined injuries from sublethal amounts of an organophosphate (soman) along with hypovolemic shock, and (2) to determine the efficacy of atropine sulfate and pralidoxime (2-PAM) therapy for organophosphate poisoning when combined injuries occur. Four groups of six beagle dogs/group were used: Group V/H, vehicle administration followed by hemorrhage; Group S/H, soman administration followed by hemorrhage; Group S/A/H, soman followed by antidote (atropine and 2-PAM) and then hemorrhage; and Group S, soman only. Acetylcholinesterase (AChE) activity, hemodynamic parameters, regional blood flow, plasma enzyme, and hematological changes were monitored. Soman rapidly decreased AChE activity in RBCs, plasma, and brain tissue. Treatment with atropine and 2-PAM resulted in only slight reactivation of AChE; they helped maintain blood gases, cortisol, plasma enzymes, inspiratory volume, and blood pressure nearer baseline values. The effects of combined injuries appear to be greater than those of either injury alone. This was indicated by increased plasma lactate, plasma enzymes indicative of tissue damage (aspartate amine transferase and creatine kinase), and increased lethality in dogs subjected to both soman and hemorrhage (5/12 died). All dogs subjected to only one insult survived the 6-hr experiment.

End-tidal CO2, CO2 production, and O2 consumption as early indicators of approaching hyperthermia.

To illustrate the abilities of several physiologic events to indicate a change in metabolic status, dinitrophenol was used to induce hyperthermia. Ten dogs were divided into two groups, one being mechanically ventilated and the other allowed to breathe spontaneously. End-tidal CO2 (ETCO2) and CO2 production, O2 consumption, mean blood pressure, and rectal temperature were monitored continuously in both groups. Respired volume was measured with a pneumotachograph. An infrared-absorption CO2 analyzer measured inspired and expired CO2 concentrations. An ultraviolet-absorption analyzer measured inspired and expired O2 concentrations. Of the physiologic events measured, CO2 production and O2 consumption were the earliest and most reliable indicators of increased metabolism and consequent approaching hyperthermia in the spontaneously breathing and mechanically ventilated animals. In the spontaneously breathing animals ETCO2 transiently decreased due to transient tachypnea. In the mechanically ventilated animals ETCO2 increased steadily. Mean blood pressure increased more in the mechanically ventilated animals than in the spontaneously breathing animals. The increase in rectal temperature required 6 minutes or more to occur, whereas the increases in CO2 production and O2 consumption appeared in only about 2 minutes. It is concluded that ETCO2 is a reliable indicator of increased metabolism in mechanically ventilated subjects only, but CO2 production and O2 consumption are excellent indicators of increasing metabolism in spontaneously breathing and mechanically ventilated subjects.

Oxygen uptake and mean blood pressure as indicators of induced hyperthermia.

This dog study was designed to identify which of two measurements (oxygen consumption, mean blood pressure) tracked the onset of hyperthermia as reflected by rectal temperature. The animals were anesthetized, paralyzed, and mechanically ventilated. Hyperthermia was induced with 2,4-dinitrophenol (5 mg/kg) injected intravenously in 5 dogs. It was found that the best and earliest predictor of approaching hyperthermia was the increase in oxygen consumption, which increased 10% in 1.72 min. Mean blood pressure was an insensitive indicator of approaching hyperthermia. Rectal temperature, not surprisingly, was found to be a late and undependable early indicator of developing hyperthermia, requiring about 15 minutes to exhibit a definite increase. It is concluded that among these indicators, monitoring oxygen consumption (ml/min) is the most reliable way to identify a metabolic change such as incipient hyperthermia.

End-tidal carbon dioxide concentration, carbon dioxide production, heart rate, and blood pressure as indicators of induced hyperthermia.

In 4 spontaneously breathing, barbiturate-anesthetized dogs, hyperthermia was induced with 2,4-dinitrophenol while rectal temperature, heart rate, mean blood pressure, end-tidal carbon dioxide, and carbon dioxide production (milliliters per minute) were measured continuously. The latter was determined with a pneumotachygraph (to obtain respired volume) and an infrared carbon dioxide analyzer that measured inspired and expired carbon dioxide concentration. Of the five physiologic measurements, the increase in carbon dioxide production preceded the increase in rectal temperature by more than 120 seconds. End-tidal carbon dioxide was an unreliable indicator in the spontaneously breathing animal of approaching hyperthermia during spontaneous breathing due to a transient tachypnea, which decreased end-tidal carbon dioxide. The carbon dioxide production (milliliters per minute) increased immediately and reached three to five times the control value. Blood pressure and heart rate were insensitive indicators of approaching hyperthermia.

Impedance cardiography by use of a spot-electrode array to track changes in cardiac output in anesthetized dogs.

Transthoracic impedance cardiography is a noninvasive method to determine changes in cardiac output on the basis of the cardiac-induced impedance change measured across the thorax. In this report, we describe a new, easily applied, tetrapolar spot-electrode configuration for use in canine transthoracic impedance cardiography. The array is a convenient alternative to use of the traditional circumferential band-electrode array which, in the dog, is prohibitive because of the extensive skin preparation required. The spot-electrode array was used to compare changes in cardiac output measured by transthoracic impedance cardiography, with changes measured by a reference indicator-dilution technique. A spot-electrode array, composed of 4 standard ECG electrodes, was used to measure transthoracic impedance in 10 anesthetized dogs. Variations in cardiac output were produced by controlled hemorrhage (200- to 250-ml increments). Simultaneous reference measurements of cardiac output were made before hemorrhage (control) and at each level of hemorrhage, using the saline-dilution method. The beat-by-beat impedance changes were measured by use of a Minnesota impedance cardiograph, which also recorded the first derivative of impedance (dZ/dt). An index of cardiac output was defined as the product of the maximal value of the first time derivative of impedance, ejection time, and heart rate for each beat during inscription of a saline-dilution curve. The average of the beat-by-beat indices was calculated and then normalized relative to the initial control value. Linear regression analysis was performed to evaluate the correlation of the index of cardiac output with the reference cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of an electrically activated valve to control preload and provide maximal muscle blood flow with a skeletal-muscle ventricle.

A new method for optimally loading a skeletal muscle-wrapped pouch to act as a blood pump is described. The method takes advantage of the fact that the high preload pressure required for a forceful contraction needs to be present for only a short time. By using an electrically controlled valve to delay pouch filling until just before muscle contraction, pouch diastolic pressure can be kept low, which in turn maintains a high muscle capillary blood flow. The intrapouch precontraction pressure can be controlled by selecting the appropriate valve-open time (VOT). The pumping capabilities of untrained rectus abdominis and latissimus dorsi muscles were evaluated using a hydraulic circulatory system in a ten dog study (weight range 20-32.7 kg). The afterload was constant at 100 mmHg, and the pouch precontraction pressure, selected by choice of the VOT, was the test variable. It was found that for maximum pouch output, a precontraction pressure of 60-100 mmHg was required, being attained in this hydraulic model with a VOT of 400-500 msec. Typical pouch outputs were 400-600 mL/min with a muscle contraction rate of 40/min. Muscle capillary blood flow, measured with a periarterial electromagnetic flowmeter, varied inversely with pouch diastolic pressure and was near zero during tetanic muscle contraction. In one animal, a pouch output of 200 mL/min or more was maintained for more than 20 hours of continuous pumping without fatigue. In a related experiment, the method was applied to pump blood in a 32.7 kg dog, in which the muscle-wrapped pouch was connected between the descending thoracic aorta and the abdominal aorta. A pouch output of about 400 mL/min was obtained when the muscle was contracted 30 times/min and the VOT was 400 msec. This flow represented about 20% of the animal's cardiac output. This study demonstrates that by delaying pouch filling until just before the muscle is to be contracted, a low pouch diastolic pressure can be maintained, thereby maximizing muscle capillary blood flow and, in turn, providing the best opportunity for prolonged pumping.