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This article discusses the importance of resuscitation guidelines in improving outcomes for cardiac arrest patients. It highlights the evolution of these guidelines over time, with a shift towards prioritizing circulation through prompt cardiopulmonary resuscitation (CPR) over airway management. The article also presents findings from a study that used thoracic bioimpedance technology to measure the effectiveness of bag-valve-mask ventilation during resuscitation efforts. The study found that adequate ventilation was associated with higher rates of survival and favorable neurological outcomes. While the study has some limitations, it suggests that attention to each aspect of resuscitation, including ventilation, may be crucial in saving more lives. [Extracted from the article]

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

Supplemental Digital Content is available in the text. Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non–CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk. [ABSTRACT FROM AUTHOR]

Background: Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in coronavirus disease 2019 (COVID-19). We aimed to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared with acute respiratory distress syndrome (ARDS) unrelated to COVID-19., Methods: We included intubated patients with COVID-19 from 5 hospitals between March 15 and June 11, 2020, with troponin levels assessed. We compared them with patients from a cohort study of myocardial injury in ARDS and performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. In addition, we performed linear regression to identify clinical factors associated with myocardial injury in COVID-19., Results: Of 243 intubated patients with COVID-19, 51% had troponin levels above the upper limit of normal. Chronic kidney disease, lactate, ferritin, and fibrinogen were associated with myocardial injury. Mortality was 22.7% among patients with COVID-19 with troponin under the upper limit of normal and 61.5% for those with troponin levels >10 times the upper limit of normal ( P <0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex, and multisystem organ dysfunction. Compared with patients with ARDS without COVID-19, patients with COVID-19 were older and had higher creatinine levels and less favorable vital signs. After adjustment, COVID-19-related ARDS was associated with lower odds of myocardial injury compared with non-COVID-19-related ARDS (odds ratio, 0.55 [95% CI, 0.36-0.84]; P =0.005)., Conclusions: Myocardial injury in severe COVID-19 is a function of baseline comorbidities, advanced age, and multisystem organ dysfunction, similar to traditional ARDS. The adverse prognosis of myocardial injury in COVID-19 relates largely to multisystem organ involvement and critical illness.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

Background: The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied., Methods: A multicenter retrospective cohort study of infants undergoing neonatal ASO between January 2010 and September 2015 at hospitals contributing data to the Pediatric Health Information Systems database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied with multivariable mixed-effects models., Results: Over the study period, 2159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of ASO varied broadly. At the subject level, older age at ASO was associated with higher mortality risk (age >6 days: odds ratio, 1.90; 95% CI, 1.11-3.26; P=0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (odds ratio, 0.32; 95% CI, 0.17-0.59; P<0.001), cost, and length of stay. Later hospital median age at ASO was associated with higher odds of mortality (odds ratio, 1.15 per day; 95% CI, 1.02-1.29; P=0.03), longer length of stay ( P<0.004), and higher cost ( P<0.001). Other hospital factors were not independently associated with the outcomes of interest., Conclusions: There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine whether modifying practice on the basis of the observed associations translates into improved outcomes.

Background: The 2010 guidelines for cardiopulmonary resuscitation allow 5 seconds to give 2 breaths to deliver sufficient chest compressions and to keep perfusion pressure high. This study aims to determine whether the recommended short interruption for ventilations by trained lay rescuers and first responders can be achieved and to evaluate its consequence for chest compressions and survival., Methods and Results: From a prospective data collection of out-of-hospital cardiac arrest, we used automatic external defibrillator recordings of cardiopulmonary resuscitation by rescuers who had received a standard European Resuscitation Council basic life support and automatic external defibrillator course. Ventilation periods and total compressions delivered per minute during each 2 minutes of cardiopulmonary resuscitation cycle were measured, and the chest compression fraction was calculated. Neurological intact survival to discharge was studied in relation to these factors and covariates. We included 199 automatic external defibrillator recordings. The median interruption time for 2 ventilations was 7 seconds (25th-75th percentile, 6-9 seconds). Of all rescuers, 21% took <5 seconds and 83% took <10 seconds for a ventilation period; 97%, 88%, and 63% of rescuers were able to deliver >60, >70, and >80 chest compressions per minute, respectively. The median chest compression fraction was 65% (25th-75th percentile, 59%-71%). Survival was 25% (49 of 199), not associated with long or short ventilation pauses when controlled for covariates., Conclusions: The great majority of rescuers can give 2 rescue breaths in <10 seconds and deliver at least 70 compressions in a minute. Longer pauses for ventilations are not associated with worse outcome. Guidelines may allow longer pauses for ventilations with no detriment to survival.

Background: The importance of clinical presentation and pretransplantation course on outcome in children with dilated cardiomyopathy listed for heart transplantation is not well defined., Methods and Results: The impact of age, duration of illness, sex, race, ventricular geometry, and diagnosis of myocarditis on outcome in 261 children with dilated cardiomyopathy enrolled in the Pediatric Cardiomyopathy Registry and Pediatric Heart Transplant Study was studied. End points included listing as United Network for Organ Sharing status 1, death while waiting, and death after transplantation. The median age at the time of diagnosis was 3.4 years, and the mean time from diagnosis to listing was 0.62±1.3 years. Risk factors associated with death while waiting were ventilator use and older age at listing in patients not mechanically ventilated (P=0.0006 and P=0.03, respectively). Shorter duration of illness (P=0.04) was associated with listing as United Network for Organ Sharing status 1. Death after transplantation was associated with myocarditis at presentation (P=0.009), nonwhite race (P<0.0001), and a lower left ventricular end-diastolic dimension z score at presentation (P=0.04). In the myocarditis group, 17% (4 of 23) died of acute rejection after transplantation., Conclusions: Mechanical ventilator use and older age at listing predicted death while waiting, whereas nonwhite race, smaller left ventricular dimension, and myocarditis were associated with death after transplantation. Although 97% of children with clinically or biopsy-diagnosed myocarditis at presentation survived to transplantation, they had significantly higher posttransplantation mortality compared with children without myocarditis, raising the possibility that preexisting viral infection or inflammation adversely affects graft survival.

Background: Experience with the use of biventricular assist device (BiVAD) support to bridge small children to heart transplantation is limited., Methods and Results: We used BIVAD support (Berlin EXCOR) in 9 pediatric heart transplant candidates from 4/05 to 7/07. The median patient age was 1.7 years (12 days to 17 years). The median patient weight was 9.4 kg (3 to 38 kg). All children were supported with multiple intravenous inotropes+/-mechanical ventilation (6) or ECMO (3) before BiVAD implantation. All had significant right ventricular dysfunction. The median pulmonary vascular resistance index (Rpi) was 6.0 WU/m(2). Eight patients were successfully bridged to heart transplantation after a median duration of BiVAD support of 35 days (1 to 77 days). One death occurred after 10 days of support from perioperative renal failure in a 3 kg infant. Five patients required at least 1 blood pump change. One patient had a driveline infection requiring treatment. There were no acute neurological complications, no thromboembolic events, and no bleeding complications. In 2 patients with Rpi >10 WU/m(2) unresponsive to pulmonary vasodilator therapy, Rpi dropped to 1.4 and 4.6 WU/m(2), after 33 and 41 days of support, respectively. All 8 survivors underwent successful heart transplantation. Of 5 patients supported >30 days, 3 developed an extremely elevated (>90%) panel reactive antibody by ELISA that was not confirmed by other methods; none had a positive donor-specific retrospective crossmatch. There was 1 episode of rejection (with hemodynamic compromise) in the 8 transplanted patients. Rpi was normal (<3 WU/m(2)) without pulmonary vasodilators in all patients within 3 months after transplant. There have been no deaths after transplant with a median follow-up of 19 months., Conclusions: BiVAD support can effectively be used in small children as a bridge to heart transplantation and can be accomplished with low mortality and morbidity. BiVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance. Surveillance for HLA antibody sensitization during BiVAD support may be complicated by the development of non-HLA antibodies which may not reflect true HLA presensitization.

Background: The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients., Methods and Results: A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation., Conclusions: Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.

Background: After modifications in our perioperative management protocol, we have observed a decrease in sudden circulatory collapse after the Norwood operation. The current study examines early outcomes after the Norwood operation in our unit in an attempt to identify variables that may have altered the risk of unexpected circulatory collapse., Methods and Results: We studied 105 consecutive neonates who underwent a Norwood operation in our institution. Our treatment protocol has changed in the past 3 years to include the use of alpha-blockade with phenoxybenzamine (POB) for systemic afterload reduction and selective cerebral perfusion. Forty-eight infants had selective cerebral perfusion. Forty-two infants received POB. Sixty patients had hypoplastic left heart syndrome. There was no difference in age, diagnosis, number of neonates with weight <2.5 kg, aortic size diameter <2 mm, highest preoperative lactate level, and shunt size indexed to body weight among patients with or without use of POB. Twenty-five infants had circulatory collapse during the first 72 hours. Twelve of them could be explained by technical issues. Thirteen others who appeared clinically stable had early sudden circulatory collapse without an apparent cause. Sixteen out of 25 neonates died. Of those with technical problems, 8 out of 12 died. Based on the hazard function, 3 incremental risk factors for early circulatory collapse were technical issue at operation (P<0.001), longer cross-clamp time (P<0.007), and no use of POB (P<0.002). For a technically successful operation, freedom from circulatory collapse at 72 hours is 95% with the use of POB versus 69% without (P<0.002). Diagnosis, aortic size, atrioventricular valve function, birth weight, age at operation, and total circulatory arrest time and were not predictive of early sudden circulatory collapse., Conclusions: Recent changes in our treatment protocol have resulted in a decrease incidence of sudden circulatory collapse after the Norwood operation. Optimal surgical technique is the most important predictor of early survival. The use of aggressive afterload reduction with POB reduced the risk of early sudden arrest.

Background: Both alpha1- and beta-adrenergic agonists increase the severity of global myocardial ischemic injury. We hypothesized that combined beta- and alpha1-adrenergic blockade would improve initial resuscitation and postresuscitation myocardial and neurological functions. We further hypothesized that the resulting alpha2-actions of relatively brief duration would favor improved functions compared with the more prolonged effect of nonadrenergic vasopressin., Methods and Results: Three groups of 5 male domestic pigs weighing 37+/-3 kg were investigated. Ventricular fibrillation was untreated for 7 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections of equipressor doses of (1) epinephrine, (2) epinephrine in which both alpha1- and beta-adrenergic effects were blocked by previous administration of prazosin and propranolol, and (3) vasopressin during CPR. All but 1 animal were successfully resuscitated. After injection of epinephrine, significantly better cardiac output and fractional area change, together with lesser increases in troponin I, were observed after alpha1- and beta-adrenergic blockade. Postresuscitation neurological function was also improved after alpha1- and beta-block in comparison with unblocked epinephrine and after vasopressin., Conclusions: Equipressor doses of epinephrine, epinephrine after alpha1- and beta-adrenergic blockade, and vasopressin were equally effective in restoring spontaneous circulation after prolonged ventricular fibrillation. However, combined alpha1- and beta-adrenergic blockade, which represented a predominantly selective alpha2-vasopressor effect, resulted in improved postresuscitation cardiac and neurological recovery.

Background: Severe acute respiratory syndrome (SARS) is characterized by an overaggressive immune response. Myocardial performance may be impaired in cytokine-mediated immune reactions., Methods and Results: Forty-six patients with established clinical diagnosis of SARS were studied prospectively. Transthoracic echocardiographic examinations were done at the acute stage of infection and 30 days later. Among them, 14 patients required mechanical ventilation. The clinical course, laboratory data, SARS-CoV antibody titers, and results of reverse transcriptase-polymerase chain reaction were studied. Significantly higher left ventricular index of myocardial performance (IMP) (0.42+/-0.13 versus 0.33+/-0.09, P<0.001), longer isovolumic relaxation time (102.9+/-15.7 versus 81.6+/-14.7 ms, P<0.001), lower flow propagation velocity (69.6+/-15.7 versus 83.8+/-19.7 cm/s, P=0.011), and Doppler-derived cardiac output (4.69+/-1.01 versus 5.49+/-1.04 L/min, P<0.001) were observed during acute infection when compared with those at 30 days. No significant valvular disease or pulmonary hypertension was found. At baseline, a lower mean left ventricular ejection fraction (LVEF) (65.3+/-12.8% versus 71.4+/-5.7%, P=0.03) and a higher mean IMP (0.51+/-0.11 versus 0.40+/-0.12, P=0.017) were found in patients who required mechanical ventilation. A decrease in LVEF correlated moderately with an elevated lactate dehydrogenase level (r=-0.605, P<0.001), whereas a higher IMP correlated weakly with an increase in creatine kinase level (r=0.38, P=0.016). Histological examination of the heart in the patient with the lowest EF (30.2%) revealed no interstitial lymphocytic infiltrate or myocyte necrosis., Conclusions: Subclinical diastolic impairment without systolic involvement was observed in patients with SARS. This impairment may be reversible on clinical recovery.

Background: Left and right carotid baroreflex afferents participate in generating the spontaneous variability of heart rate (HR), arterial pressure (AP), and muscle sympathetic nerve activity (MSNA), but the relative contribution of each side is unclear. Pathophysiological conditions unilaterally affecting carotid baroreceptor function might result in abnormal changes of HR, AP, and MSNA variability, thus markedly affecting prognosis. We tested the hypothesis that unilateral carotid baroreceptor perturbation might differentially affect HR, AP, and MSNA variability compared with stimulation of the opposite side., Methods and Results: In 12 healthy volunteers, 4 sinusoidal neck suction procedures (0.1 Hz, from 0 to -50 mm Hg) were applied at the right, left, and combined right and left sides of the neck, in concordance or with phase opposition. Respiration was controlled at 0.25 Hz. Power spectrum analysis assessed the changes in the 0.1-Hz oscillatory component of the R-R interval, systolic AP (SAP), and MSNA variability induced by rhythmic baroreceptor stimulation. Mean R-R interval, SAP, and MSNA were unchanged during all procedures. The increase of the 0.1-Hz component of R-R and SAP variability during right and combined right and left carotid baroreceptor stimulation was greater than the changes induced by left-sided stimulation. The increase in the 0.1-Hz oscillatory component of MSNA variability was similar during all neck suction procedures., Conclusions: Right carotid baroreflex loading was as efficient as bilateral stimulation and more effective than left carotid suction in modulating R-R and SAP variability. There was no asymmetry in neural sympathetic discharge responses after single-sided carotid baroreceptor stimulation.

Background: Phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil) are a novel, orally active approach to the treatment of pulmonary arterial hypertension. The role of natriuretic peptides in the response to sildenafil was examined in mice lacking NPR-A, a guanylyl cyclase-linked natriuretic peptide receptor, in which pulmonary hypertension was induced by hypoxia., Methods and Results: Mice homozygous for NPR-A (NPR-A+/+) and null mutants (NPR-A-/-) were studied. Sildenafil inhibited the pressor response to acute hypoxia in the isolated perfused lungs of both genotypes. This effect was greater in the presence of atrial natriuretic peptide in the perfusate in NPR-A+/+ mice but not NPR-A-/- animals. In vivo, NPR-A mutants had higher basal right ventricular (RV) systolic pressures (RVSPs) than did NPR-A+/+ mice, and this was not affected by 3 weeks of treatment with sildenafil (25 mg x kg(-1) x d(-1)). Both genotypes exhibited a rise in RVSP and RV weight with chronic hypoxia (10% O2 for 21 days); RVSP and RV weight were reduced by continuous sildenafil administration in NPR-A+/+ mice, but only RVSP showed evidence of a response to the drug in NPR-A-/- mice. The effect of sildenafil on hypoxia-induced pulmonary vascular muscularization and cyclic GMP levels was also blunted in NPR-A-/- mice., Conclusions: The natriuretic peptide pathway influences the response to PDE5 inhibition in hypoxia-induced pulmonary hypertension, particularly its effects on RV hypertrophy and vascular remodeling.

Background: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models., Methods and Results: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma, and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred., Conclusions: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Background: While unifocalization techniques have improved the treatment options in patients with pulmonary atresia, ventricular septal defect (PA-VSD), and major aortopulmonary collaterals (MAPCAs), severe airflow limitation contributes to significant early postoperative morbidity and mortality. Although this has been attributed to bronchospasm, characteristically it is refractory to bronchodilators, suggesting that other mechanisms may play a role., Methods and Results: The clinical course and preoperative angiograms of patients who underwent unifocalization were reviewed. Patients who developed airflow limitation early after surgery underwent fiberoptic bronchoscopy. In addition, the anatomy of the MAPCAs was examined in 14 heart-lung blocks from patients with PA-VSD. Twenty-two procedures were performed in 16 children. Three developed marked airflow limitation early after surgery, necessitating prolonged high-pressure ventilation. Bronchoscopy demonstrated tracheobronchial epithelial necrosis in 2 and signs of tracheobronchial ischemia in the third. Two were successfully extubated after 15 and 16 days, but the third died after 57 days of ventilatory support. Review of the preoperative angiograms demonstrated an extensive peribronchial arterial supply arising from a MAPCA in 1 of the patients who developed severe airway necrosis after unifocalization. This was also obvious in a second patient, but the MAPCA was not included in the unifocalization. In 7 autopsy specimens, MAPCAs contributed to a peribronchial or peritracheal vascular network. Dissection of the distribution of these branches in 2 specimens revealed extensive intrapulmonary peribronchial anastomoses., Conclusions: Airflow limitation early after unifocalization is related to airway ischemia resulting from interruption of the tracheobronchial blood supply during mobilization of MAPCAs.

Background: Pulmonary capillary endothelium-bound (PCEB) angiotensin-converting ectoenzyme (ACE) activity alteration is an early, sensitive, and quantifiable lung injury index in animal models. We hypothesized that (1) PCEB-ACE alterations can be found in patients with acute lung injury (ALI) and (2) PCEB-ACE activity correlates with the severity of lung injury and may be used as a quantifiable marker of the underlying pulmonary capillary endothelial dysfunction., Methods and Results: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis of the synthetic ACE substrate (3)H-benzoyl-Phe-Ala-Pro (BPAP) in 33 mechanically ventilated, critically ill patients with a lung injury score (LIS) ranging from 0 (no lung injury) to 3.7 (severe lung injury) and calculated the kinetic parameter A(max)/K(m). Both parameters decreased early during the ALI continuum and were inversely related to APACHE II score and LIS. Hydrolysis decreased with increasing cardiac output (CO), whereas 2 different patterns were observed between CO and A(max)/K(m)., Conclusions: PCEB-ACE activity decreases early during ALI, correlates with the clinical severity of both the lung injury and the underlying disease, and may be used as a quantifiable marker of underlying pulmonary capillary endothelial dysfunction.

Background: Bystander cardiopulmonary resuscitation (CPR) without assisted ventilation may be as effective as CPR with assisted ventilation for ventricular fibrillatory cardiac arrests. However, chest compressions alone or ventilation alone is not effective for complete asphyxial cardiac arrests (loss of aortic pulsations). The objective of this investigation was to determine whether these techniques can independently improve outcome at an earlier stage of the asphyxial process., Methods and Results: After induction of anesthesia, 40 piglets (11.5+/-0.3 kg) underwent endotracheal tube clamping (6.8+/-0.3 minutes) until simulated pulselessness, defined as aortic systolic pressure <50 mm Hg. For the 8-minute "bystander CPR" period, animals were randomly assigned to chest compressions and assisted ventilation (CC+V), chest compressions only (CC), assisted ventilation only (V), or no bystander CPR (control group). Return of spontaneous circulation occurred during the first 2 minutes of bystander CPR in 10 of 10 CC+V piglets, 6 of 10 V piglets, 4 of 10 CC piglets, and none of the controls (CC+V or V versus controls, P<0.01; CC+V versus CC and V combined, P=0.01). During the first minute of CPR, arterial and mixed venous blood gases were superior in the 3 experimental groups compared with the controls. Twenty-four-hour survival was similarly superior in the 3 experimental groups compared with the controls (8 of 10, 6 of 10, 5 of 10, and 0 of 10, P<0.05 each)., Conclusions: Bystander CPR with CC+V improves outcome in the early stages of apparent pulseless asphyxial cardiac arrest. In addition, this study establishes that bystander CPR with CC or V can independently improve outcome.

Background: Bidirectional superior cavopulmonary connection (BSCC) may be complicated by systemic hypoxemia. Hyperventilation, which is standard therapy for postoperative hypoxemia, has opposing effects on the pulmonary and cerebral vascular beds, which are connected after BSCC. It is unknown which of these effects predominates and, therefore, whether hyperventilation improves or impairs systemic oxygenation after BSCC., Methods and Results: Twelve consecutive patients (median age, 6.4 months; age range, 6.0 to 32.0, months) undergoing BSCC were studied prospectively. Patients were studied in the intensive care unit within 6 hours of surgery and while sedated, paralyzed, and mechanically ventilated. Inotropes were not altered, and no transfusions were given. FIO2 was set at 100%, and peak end-expiratory pressure was set at 0. Each patient was studied first during normal ventilation, then during hyperventilation, and finally again during normal ventilation. Hyperventilation resulted in significant decreases in arterial PO2, systemic oxygen saturation, and transpulmonary gradient. Cerebral blood flow velocity was measured in 6 patients through transcranial Doppler sonography of the middle cerebral artery. Mean cerebral flow velocity decreased significantly during hyperventilation., Conclusions: Hyperventilation significantly impairs systemic oxygenation after BSCC. This fall in oxygenation occurs despite a decrease in transpulmonary gradient. A possible mechanism for this effect is that hyperventilation lowers arterial PCO2, raising cerebral vascular resistance, and lowering cerebral, superior vena caval, and pulmonary blood flows. Supportive evidence for this mechanism is the decrease in cerebral flow velocity that occurs during hyperventilation. After BSCC, normal ventilation rather than hyperventilation should be used to improve systemic oxygen levels.

Background: Mouth-to-mouth rescue breathing is a barrier to the performance of bystander cardiopulmonary resuscitation (CPR). We evaluated the need for assisted ventilation during simulated single-rescuer bystander CPR in a swine myocardial infarction model of prehospital cardiac arrest., Methods and Results: Steel cylinders were placed in the mid left anterior descending coronary arteries of 43 swine. Two minutes after ventricular fibrillation, animals were randomly assigned to 10 minutes of hand-bag-valve ventilation with 17% oxygen and 4% carbon dioxide plus chest compressions (CC+V), chest compressions only (CC), or no CPR (control group). Standard advanced life support was then provided. Animals successfully resuscitated received 1 hour of intensive care support and were observed for 24 hours. Five of 14 CC animals, 3 of 15 CC+V animals, and 1 of 14 controls survived for 24 hours (CC versus controls, P=.07). Myocardial oxygen delivery and consumption were greater among surviving animals than nonsurvivors but did not differ between CC and CC+V animals., Conclusions: In this acute myocardial infarction model of prehospital single-rescuer bystander CPR, assisted ventilation did not improve outcome.

Background: Mouth-to-mouth rescue breathing is a barrier to the performance of bystander cardiopulmonary resuscitation (CPR). We evaluated the need for assisted ventilation during simulated single-rescuer bystander CPR in a swine model of prehospital cardiac arrest., Methods and Results: Five minutes after ventricular fibrillation, swine were randomly assigned to 8 minutes of hand-bag-valve ventilation with 17% oxygen and 4% carbon dioxide plus chest compressions (CC + V), chest compressions only (CC), or no CPR (control group). Standard advanced life support was then provided. Animals successfully resuscitated received 1 hour of intensive care support and were observed for 24 hours. All 10 CC animals, 9 of the 10 CC + V animals, and 4 of the 6 control animals attained return of spontaneous circulation. Five of the 10 CC animals, 6 of the 10 CC + V animals, and none of the 6 control animals survived for 24 hours (CC versus controls, P = .058; CC + V versus controls, P < .03). All 24-hour survivors were normal or nearly normal neurologically., Conclusions: In this model of prehospital single-rescuer bystander CPR, successful initial resuscitation, 24-hour survival, and neurological outcome were similar after chest compressions only or chest compressions plus assisted ventilation. Both techniques tended to improve outcome compared with no bystander CPR.

Background: A low cardiac output state can complicate the postoperative course of patients undergoing Fontan-type operations and tetralogy of Fallot repair., Methods and Results: We investigated the effect of negative-pressure ventilation on cardiac output in 11 children in the early postoperative period after right heart surgery. All patients were initially ventilated with volume-cycled intermittent positive-pressure ventilation, and negative-pressure ventilation was delivered with the Hayek external high-frequency oscillator. Cardiac output was calculated by the direct Fick method, oxygen consumption being measured by respiratory mass spectrometry. Cardiac output was measured during intermittent positive-pressure ventilation and after 15 minutes of negative-pressure ventilation. Negative-pressure ventilation improved the cardiac output by a mean of 46% (P = .005). Heart rate did not change, and stroke volume increased by a mean of 48.5% (P = .005). Mixed venous saturation increased by 4.6% (P < .02), and consequently arteriovenous oxygen content difference fell significantly (P = .01). The systemic and pulmonary vascular resistances were reduced significantly during negative-pressure ventilation (P < .05 and P < .03, respectively)., Conclusions: Negative-pressure ventilation improves cardiac output in children after total cavopulmonary connection and tetralogy of Fallot repair and may prove to be an important therapeutic option in children with the low cardiac output state.

Background: It is widely held that the postoperative course of patients with hypoplastic left heart syndrome (HLHS) after stage 1 palliation is characterized by hemodynamic instability, which in part may be due to excessive pulmonary blood flow. Hence, avoidance of alkalosis and the use of minimally oxygen-enriched inspiratory gas are thought by many to be important, although there is little pertinent published data. This study was undertaken to characterize the postoperative course and to determine whether the FIO2 and blood pH are related to indices of hemodynamic stability in these infants., Methods and Results: The postoperative course of 25 consecutive infants undergoing first stage palliation for HLHS were retrospectively reviewed and the following data were obtained: arterial pressure, arterial blood gas measurements, the inotropic agents used, and multiple respiratory parameters. There was one operative death, and 2 patients died within 2 days, but 22 were extubated (mean, 5.2 +/- 4.1 days after surgery). Hospital mortality was 24%. Mean pH was > or = 7.51 for the first 9 hours after surgery and was > or = 7.45 for the entire period. The mean FIO2 was > or = 50% for the first 18 hours. The PaO2 was appropriate (37 +/- 6 mm Hg at 1 hour after surgery, increasing to 45 +/- 5 mm Hg by hour 73). Only modest inotropic support was needed to maintain appropriate blood pressure., Conclusions: These data suggest that neither alkalosis nor relatively high inspired oxygen necessarily cause hemodynamic instability in these patients. To what extent these results are generalizable is unclear, but they suggest that there is nothing inherent with HLHS that mandates postoperative hemodynamic instability or unacceptable mortality.

Background: The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest., Methods and Results: Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P < .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P < .002)., Conclusions: In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.

Background: Important in the postoperative management of neonates with single-ventricle complexes, such as hypoplastic left heart syndrome and pulmonary atresia with intact ventricular septum, is the fact that the pulmonary circulation is connected to the systemic circulation via a shunt. The distribution of flow to the pulmonary and systemic vascular beds depends directly on the pulmonary-to-systemic vascular resistance ratio. Changes in this ratio result in alterations in flow that have an impact on survival., Methods and Results: PICO2 has a potent effect on pulmonary vascular resistance. In this study, the addition of CO2 to inspired gas (PICO2) is assessed as a means of modulating the ratio of pulmonary-to-systemic vascular resistance and thus flow, while avoiding the consequences of hypoventilation. Thirteen neonatal piglets (age, 17 to 30 days) were subjected to atrial septectomy, patch closure of the tricuspid valve, and creation of a 4-mm systemic-to-pulmonary arterial shunt to mimic the physiology of single-ventricle complexes. Pulmonary and systemic flows; aortic, pulmonary artery, and atrial pressures; and arterial blood gases were measured with the addition of different levels of CO2 to the inspired gases (PICO2 = 0 to 35 mmHg). In all animals, pulmonary vascular resistance (PVR) increased in direct correlation with PICO2. In group 1 (n = 8), PVR increased in direct correlation with PICO2 and PACO2, and inversely with respect to pH (r = .98, .74, and .83, respectively). Group 2 animals (n = 5) received infusions of Tham to buffer hydrogen ion and compensate for respiratory acidosis. PVR again increased in direct correlation with FICO2 (r = .97). In both groups, systemic vascular resistance (SVR) was less directly influenced by FICO2 (r = .53)., Conclusions: CO2 exerts a vasoactive influence on pulmonary vasculature that is largely independent of SVR and pH. Regulating PICO2 is an effective means of achieving a favorable ratio of pulmonary-to-systemic vascular resistance and thus flow in the fragile physiology encountered in neonates with single-ventricle complexes.

Background: Prompt initiation of bystander cardiopulmonary resuscitation (CPR) improves survival. Basic life support with mouth-to-mouth ventilation and chest compressions is intimidating, difficult to remember, and difficult to perform. Chest compressions alone can be easily taught, easily remembered, easily performed, adequately taught by dispatcher-delivered telephone instruction, and more readily accepted by the public. The principal objective of this study was to evaluate the need for ventilation during CPR in a clinically relevant swine model of prehospital witnessed cardiac arrest., Methods and Results: Thirty seconds after ventricular fibrillation, swine were randomly assigned to 12 minutes of chest compressions plus mechanical ventilation (group A), chest compressions only (group B), or no CPR (group C). Standard advanced cardiac life support was then provided. Animals successfully resuscitated were supported for 2 hours in an intensive care setting, and then observed for 24 hours. All 16 swine in groups A and B were successfully resuscitated and neurologically normal at 24 hours, whereas only 2 of 8 group C animals survived for 24 hours (P < .001, Fisher's exact test). One of the 2 group C survivors was comatose and unresponsive., Conclusions: In this swine model of witnessed prehospital cardiac arrest, the survival and neurological outcome data establish that prompt initiation of chest compressions alone appears to be as effective as chest compressions plus ventilation and that both techniques of bystander CPR markedly improve outcome compared with no bystander CPR.

Background: In patients with transposition of the great arteries with low left ventricular pressure, pulmonary artery banding with aortopulmonary shunt placement has been advocated to "prepare" the left ventricle for systemic work before an arterial switch operation., Methods and Results: In 28 patients, this preparatory procedure was performed with one death. A successful arterial switch operation was performed at a median of 7 days later in 24 of 27 survivors; one child had a Senning performed, and two others died. During this interval period, the left ventricular-to-right ventricular pressure ratio increased from 48 +/- 8% to 98 +/- 19%, and left ventricular mass (indexed for body surface area) increased from 46 +/- 17 to 72 +/- 23 g/m2. After the preparatory procedure, the initial postoperative period was frequently characterized by a low-output syndrome of variable length and severity. Prolonged mechanical ventilation, extended inotropic support, and/or a significant metabolic acidosis was present in 21 of 28 patients in the immediate postoperative period., Conclusions: The low-output syndrome is most likely due to a combination of acute (fixed) right ventricular volume overload from the shunt and acute (transient) left ventricular dysfunction from the pulmonary artery band. This low-output syndrome should be anticipated following the preparatory procedure.

Background: To determine how the tissues that surround the heart affect diastolic and systolic function during the perinatal period, we studied the pressure-diameter relation of the left ventricle in partially delivered fetal lambs., Methods and Results: We anesthetized (1.5-2.0% halothane, balance O2) and ventilated six pregnant ewes (142-144 days of gestation) and then partially delivered each lamb by cesarean section. Each lamb was instrumented to record left ventricular anteroposterior diameters (endocardial ultrasonic transducers), pericardial pressure (liquid-containing balloon), and left ventricular pressure (transducer-tipped catheter). Left ventricular pressure-diameter relations were recorded under three conditions: initially, with a closed chest and closed pericardium (before ventilation); second, after interruption of the umbilical circulation and 1 hour of ventilation; and finally, when the lungs and the pericardium were retracted from the heart. Pericardial pressure (recorded at a common diameter, i.e., the maximal end-diastolic diameter recorded before ventilation) decreased by 48% after 1 hour of ventilation (p < 0.05). After ventilation, left ventricular anteroposterior diameters were 4-5% greater (p < 0.05) at each end-diastolic pressure compared (12.5, 15.0, 17.5, and 20 mm Hg). Thus, ventilation appeared to increase left ventricular diastolic compliance. Contractility also appeared to increase after ventilation when evaluated using ventricular stroke work as a function of end-diastolic pressure as preload. When we used a more appropriate measure of preload (i.e., transmural end-diastolic pressure), ventilation did not change left ventricular diastolic compliance or contractility. Thus, left ventricular systolic function increased because of an increase in preload., Conclusions: The tissues surrounding the fetal heart significantly augment pericardial pressure and limit left ventricular preload. The initiation of ventilation reduces pericardial pressure, increases left ventricular preload, and increases left ventricular systolic function. At birth, a decrease in pericardial pressure and the resulting increase in preload may help increase left ventricular output through the Frank-Starling mechanism.

Pulmonary vascular resistance is an important determinant of cardiac output after the Fontan procedure and is adversely affected by elevated mean airway pressure. High-frequency jet ventilation (HFJV) is an alternate form of mechanical ventilation which supports gas exchange at lower mean airway pressure. This study was performed to determine if HFJV could lower mean airway pressure and pulmonary vascular resistance and result in an increase in cardiac output after the Fontan procedure. We prospectively evaluated 13 patients ranging in age from 0.9 to 8.5 years (mean, 3.9 years) and in weight from 6.2 to 20.1 kg (mean, 13.9 kg). Right atrial, left atrial and pulmonary artery catheters were used to measure hemodynamic parameters. Cardiac index was measured by dye dilution technique, and pulmonary vascular resistance was calculated. The patients were stabilized on mechanical ventilation to achieve a PaCO2 = 30 +/- 5 mm Hg, and baseline hemodynamic and respiratory measurements were made. HFJV was begun at settings adjusted to achieve similar gas exchange. Respiratory and hemodynamic measurements were repeated after 30-60 minutes of HFJV. Mechanical ventilation was then resumed at baseline settings, and measurements were repeated 0.5-1 hour later. There was no significant change in gas exchange. HFJV resulted in a 50% reduction in mean airway pressure (9.2 +/- 0.2 cm H2O to 4.6 +/- 0.1 cm H2O, p less than 0.001), a 59% reduction in pulmonary vascular resistance (3.82 +/- 0.36 to 1.52 +/- 0.16 Woods units, p less than 0.001), and a 25% increase in cardiac index (2.32 +/- 0.12 l/min/m2 to 2.91 +/- 0.12 l/min/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The finding that blood flow during external chest compression may be due to increased intrathoracic pressure, and the subsequent reporting of increased carotid blood flow with simultaneous ventilation and chest compression or with abdominal binding during CPR ignited a flurry of investigations into alternative approaches to CPR. A number of alterations of the conventional CPR technique were proposed, many resulting in improved hemodynamics when compared with standard CPR techniques in the same subject. However, some of the proposed methods increased cerebral blood flow but decreased myocardial perfusion. Others improved systolic pressures but decreased vital organ blood flow. More importantly, most studies with survival as an end point failed to show a benefit when alternative approaches to CPR were used. Therefore, it is unlikely that there will be significant changes in the recommendations for the use of adjuncts during CPR. Not all studies support the conclusion that blood flow during closed-chest compression is secondary to increased intrathoracic pressure. It is probable that in man there is a spectrum. In some individuals the predominant mechanism of blood flow during CPR may be cardiac and/or vascular compression, and in others flow may be secondary to an increased intrathoracic pressure.

To assess the effects of i.v. injection of morphine, 0.5 mg/kg, hemodynamic studies were performed on 24 critically ill patients under controlled ventilation. An esophageal balloon was used to estimate intrapleural pressure and transmural cardiac filling pressures were calculated. After injection of morphine, there were significant decreases in heart rate (13%), cardiac index (18%), stroke index (17%) and arterial pressure (15%) and there was a nonsignificant increase in esophageal pressure (15%). Transmural cardiac filling pressures decreased significantly (21% for the pulmonary wedge pressure); intravascular filling pressures were unchanged. Oxygen consumption decreased significantly, by 21%, in 10 patients with initially elevated oxygen consumption and by 9% in 14 patients with initially normal oxygen consumption. The oxygen extraction ratio was unchanged, suggesting that the decrease in oxygen consumption was caused by decreased oxygen demand rather than by inadequate oxygen delivery. These results indicate that the hemodynamic effects of morphine (0.5 mg/kg) administered to critically ill patients were associated with a significant decrease in oxygen consumption, which probably reflected sedation and analgesia.

We studied left ventricular performance and contractility after volume loading in lambs at 122 days (group I, n = 9) and 139 days gestational age (group II, n = 9) and in 8-day-old full-term lambs (group III, n = 7). All were mechanically ventilated; each preterm lamb was treated with surfactant to stabilize pulmonary function and the ductus arteriosus was occluded with an inflated catheter balloon. Cineangiograms, left ventricular and vascular pressures, and the isovolumetric index of contractility, first derivative of left ventricular pressure (dP/dt), were recorded before and after three successive whole blood volume infusions of 10 ml/kg (total 30 ml/kg). The left ventricular end-diastolic volume per kilogram and stroke volume per kilogram increased significantly in all groups after volume infusion; these measurements and heart rate and systemic vascular resistance did not differ significantly between the groups either before or after the infusions. The left ventricular peak dP/dt did not change significantly within the groups during the volume infusions. The left ventricular stroke work was greatest in full-term animals and increased significantly in all groups after volume infusion. Thus, the left ventricles of the preterm and full-term lambs had quantitatively similar Frank-Starling responses and there was no increase in contractility during the infusions of whole blood. However, the left ventricle of the full-term lamb is capable of generating greater stroke work than that of the preterm lamb. These findings may contribute to the understanding of development aspects of postnatal circulatory adaptation.

Myocardial and cerebral blood flow can be generated during cardiac arrest by techniques that manipulate intrathoracic pressure. Augmentation of intrathoracic pressure by high-pressure ventilation simultaneous with compression of the chest in dogs has been shown to produce higher flows to the heart and brain, but has limited usefulness because of the requirement for endotracheal intubation and complex devices. A system was developed that can produce high intrathoracic pressure without simultaneous ventilation by use of a pneumatically cycled vest placed around the thorax (vest cardiopulmonary resuscitation [CPR]). The system was first tested in a short-term study of the maximum achievable flows during arrest. Peak vest pressures up to 380 mm Hg were used on eight 21 to 30 kg dogs after induction of ventricular fibrillation and administration of epinephrine. Microsphere-determined myocardial blood flow was 108 +/- 17 ml/min/100 g (100 +/- 16% of prearrest flow) and cerebral flow was 51 +/- 12 ml/min/100 g (165 +/- 39% of prearrest). Severe lung or liver trauma was noted in three of eight dogs. If peak vest pressure was limited to 280 mm Hg, however, severe trauma was no longer observed. A study of the hemodynamics during and survival from prolonged resuscitation was then performed on three groups of seven dogs. Vest CPR was compared with manual CPR with either conventional (300 newtons) or high (430 newtons) sternal force. After induction of ventricular fibrillation, each technique was performed for 26 min. Defibrillation was then performed.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effect of phasic pulmonary afferent information on heart rate (HR) during a progressive reduction in oxygen saturation (SaO2). The Hering-Breuer reflex was evaluated with the use of the ratio of apnea duration after lung inflation to the preceding expiratory time (dT). Phasic afferent activity was stopped in anesthetized, paralyzed dogs by constant-flow ventilation (CFV), a technique that removes cyclic changes in lung volume. During normocapnic (PaCO2 = 36.4 +/- 1.1 mm Hg) spontaneous breathing, there was a wide variability in HR response, with a mean delta HR/delta SaO2 (+/- SE) of 0.62 +/- 0.27 beats/min/% (values greater than 0 indicate a tachycardiac response). There was a good correlation between delta HR/delta SaO2 and dT (r = .79). Mean delta HR/delta SaO2 for the combined normocapnic and hypercapnic studies during CFV was lower (-1.32 +/- 0.19 bpm/%) than that during spontaneous breathing (0.23 +/- 0.19, p less than .0001). We suggest that the HR response to hypoxemia is strongly related to the strength of the Hering-Breuer reflex, which may explain the large interdog variability in HR responses.